Compound 48/80 (Com 48/80), a mast cell degranulator, triggers allergic reactions and has been linked to a reduced risk of skin cancer. This study investigated the potential anticancer effects of Com 48/80 using in vitro and in vivo melanoma models. In vitro, Com 48/80 significantly induced apoptosis in melanocytes through caspase activation. In the melanoma animal model experiment, Com 48/80 enhanced survival, reduced tumor volume, and downregulated melanoma-specific genes (Dct2 and Gp100), while increasing the activities of caspase-3, -8, and -9. Additionally, Com 48/80 elevated allergy-related and immune-enhancing mediators, including immunoglobulin E, histamine, interleukin (IL)-2, IL-4, IL-5, IL-6, IL-12, IL-13, IL-33, tumor necrosis factor-α, thymic stromal lymphopoietin, and interferon-γ. In the immunodeficient mice, Com 48/80 improved survival, suppressed melanoma growth, reduced immobility time, and enhanced the expression of immune mediators. Moreover, Com 48/80 significantly lowered tissue damage indicators compared to tumor control mice. These results suggest that Com 48/80 inhibits melanoma progression by inducing apoptosis and enhancing immune responses, highlighting the potential of Com 48/80 as a novel therapeutic strategy for melanoma treatment and prevention.

Mucosal melanoma (MM) is an aggressive and rare subtype of melanoma, and it is associated with poor prognosis. Surgical resection remains the mainstay of the treatment for localized disease, and different from cutaneous melanoma, the impact of adjuvant therapy has not been clearly established. We retrospectively analyzed patients with surgically resected MM from the MD Anderson Cancer Center melanoma database from January 2000 to December 2019. The univariate log-rank test and multivariate Cox regression model were used to analyze the impact of adjuvant therapy on overall survival (OS) and relapse-free survival. A total of 246 patients with localized or locally advanced MM who underwent surgical resection were included. The median OS for all patients was 4.8 years [95% confidence interval (CI), 3.6-6], with median OS for the 125 patients who received adjuvant systemic therapy was 5.7 years (95% CI, 4.0-10.2) and 4.0 years (95% CI, 2.8-6.6) for the 121 patients who had only surgery or surgery plus radiation in the subanalysis, chemotherapy was associated with a longer OS (7.3 years; 95% CI, 4.4-NA) compared to immunotherapy (5.5 years; 95% CI, 2.8-NA). Cox regression analysis demonstrated lymph node involvement, Breslow thickness, and use of adjuvant systemic therapy were considered independent factors for OS. Adjuvant systemic therapy was associated with a significant survival benefit in patients with resected MM (HR 0.53; 95% CI, 0.34-0.82; P = 0.004). However, due to the retrospective nature of the study, prospective clinical trials are warranted to determine the optimal adjuvant treatment strategy for this patient population.

Peritoneal carcinomatosis represents an exceptionally rare metastatic pattern of cutaneous malignant melanoma, occurring in fewer than 1% of cases with distant spread and typically within the first few years after primary treatment. This report presents an unusual case with a markedly prolonged disease-free interval, clinically mimicking advanced ovarian carcinoma. We report the case of a 53-year-old woman treated more than 10 years ago for stage IIB nodular melanoma with surgery and adjuvant therapy. The patient presented with progressive abdominal bloating. Imaging revealed bilateral adnexal masses, ascites, peritoneal carcinomatosis, and multiple pulmonary nodules, initially suggestive of advanced ovarian cancer. Diagnostic laparoscopy demonstrated diffuse peritoneal lesions with an atypical yellowish, soft, and nonpigmented appearance. Histology and immunohistochemistry confirmed metastatic melanoma. This case is among the few reports of peritoneal carcinomatosis from melanoma after more than a decade of remission. The prolonged disease-free interval and atypical presentation underline the heterogeneous behavior of melanoma and the need for long-term vigilance and multidisciplinary evaluation.

Patients with mucosal melanoma have lower survival rates than those with cutaneous melanoma. Recent studies have reported lower mucosal melanoma survival rates with the use of immune checkpoint inhibitors (ICIs). This study analyzed ICI treatment outcomes in patients with mucosal melanoma in a real-world context. The objective response rate, progression-free survival (PFS), and overall survival (OS) after first- and second-line ICI treatments were analyzed in a population of patients with advanced mucosal melanoma included in the observational GEM1801 study in Spain. Univariate Cox regression analysis was used to identify prognostic factors. From 1126 patients included between August 2018 and January 2024, 52 (4.6%) patients with mucosal melanoma were selected, with a median age at advanced stage diagnosis of 70 years; 50% were female. Most patients had an Eastern Cooperative Oncology Group performance status of 0 (48%). Tumors were primarily located in the lower gastrointestinal tract (40%) and the nasal cavity (35%). In the metastatic setting, 32 (62%) patients received ICI. At a median follow-up of 13.7 months, patients receiving ICI had a median PFS and OS of 9.4 [95% confidence interval (CI): 6.6-17.0] and 25.9 (95% CI: 21-not reached) months, respectively, for first-line treatment, and 5.1 (95% CI: 1.9-not reached) and 21.0 (95% CI: 11.1-not reached) months for second-line treatment. The clinical benefit of ICI treatment in mucosal melanoma is in accordance with previous clinical trials but is still limited, highlighting the need for new approaches for this patient population.

Prognosis for metastatic melanoma patients treated with immune checkpoint inhibitors (ICIs) remains heterogeneous. Although neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-eosinophil ratio (NER) are established markers, we hypothesized a neutrophil-to-lymphocyte-times-eosinophil (NLE) index would offer superior stratification. We analyzed 194 metastatic melanoma patients receiving ICIs, divided into training ( n  = 129) and validation ( n  = 65) cohorts. An optimal NLE cutoff categorized patients as NLE-low or NLE-high. Survival outcomes and objective response rate (ORR) were assessed using Kaplan-Meier, Cox regression, and logistic regression. Predictive accuracy of NLE, NLR, and NER was compared. Median overall survival was significantly longer in NLE-low versus NLE-high patients (training: 31.3 versus 6.9 months; P  = 0.011; validation: 33.5 versus 9.1 months; P  = 0.019). Median progression-free survival also improved significantly in NLE-low patients (training: 10.6 versus 3.1 months; P  = 0.029; validation: 13.7 versus 3.9 months; P  = 0.012). ORR was higher in NLE-low groups (training: 46.0% versus 13.2%; P  < 0.001; validation: 43.6% versus 18.2%; P  = 0.078). NLE demonstrated superior predictive accuracy compared with NLR and NER. The NLE index outperforms NLR and NER in predicting survival and response in metastatic melanoma patients treated with ICIs, providing a practical clinical tool.

The exact role of nevi in the development of melanoma is not yet completely understood, and it remains unknown whether de novo and nevus-associated melanoma (NAM) constitute distinct biological entities. A few studies have documented differences in histological and clinical characteristics between de novo and NAMs; however, data from Southern Europe are lacking. This study examined epidemiological and clinical data of patients who were followed up at the Melanoma Reference Center of the General Hospital of Athens G. Gennimatas from 2022 to 2024 and had been diagnosed with primary skin melanoma from 1999 to 2024. In a total of 509 primary melanomas 289 (56.8%) were nevus-associated and 220 (43.2%) de novo. NAMs were more likely to be diagnosed in patients <40 and 40-65 years old compared to de novo melanomas (P < 0.001). NAMs were more likely to develop on the trunk and the extremities compared to de novo tumors, which predominated on the head (P < 0.001). Superficial spreading melanomas were more likely to be nevus-associated, while nodular, acral lentiginous, and lentigo maligna melanomas were more likely to develop de novo (P < 0.001). NAMs were more likely to be diagnosed at earlier stages and be thinner compared to de novo tumors (P < 0.001). NAMs were also more likely not to present ulceration (P = 0.002) and to have a low mitotic rate (<3/mm2) (P < 0.001). Patients with de novo melanomas more often experienced disease progression compared to those with NAM. NAMs seem to have less aggressive behavior compared to de novo melanomas. This study highlights the differences between de novo and NAMs, adding novel information about features such as the presence of dysplastic nevi, the mitotic rate, and the disease progression that had not been investigated in previous studies.

This retrospective cohort study evaluated disparities across insurance types, racial groups, and socioeconomic status (SES) in acral lentiginous melanoma (ALM). We analyzed adults diagnosed with ALM in the National Cancer Database from 2016-2020. Cox proportional hazards model assessed associations between demographic and clinical variables with ALM-specific survival. Kaplan-Meier curves analyzed 1-, 3-, and 5-year survival. A total of 3446 patients with ALM were identified. Uninsured patients presented with advanced-stage cancers, experienced longer time to treatment, and were more likely to undergo major amputations compared with privately insured patients ( P  < 0.001). Survival analysis indicated lower probabilities for uninsured patients at 1, 3, and 5 years, although the differences did not reach statistical significance. Black patients were more likely uninsured, had higher Charlson-Deyo comorbidity scores, resided in areas of lower income and education, experienced longer time to treatment ( P  < 0.001), and had significantly lower survival at 3 and 5 years compared with White patients ( P  < 0.01). Patients in SES Q1 traveled further for care, had longer time to treatment, were less likely to be treated with Mohs surgery ( P  < 0.001), and had worse survival at 1, 3, and 5 years compared with patients in SES Q4 ( P  < 0.001). In conclusion, significant disparities in disease presentation, access to care, and health outcomes in patients with ALM exist based on insurance status, race, and SES, emphasizing the need for targeted interventions to enhance early diagnosis and equitable treatment.

Metastatic melanoma is characterized by high rates of treatment resistance. While various factors have been studied for their prognostic significance, this study evaluated the potential prognostic value of the intrinsic disorder of T-cell receptor beta (TRB) polypeptides. TRB recombination sequencing reads were extracted from tumor RNA-seq files representing The Cancer Genome Atlas, Skin Cutaneous Melanoma dataset, and genomics files representing the National Institutes of Health, phs002683 dataset. Intrinsic disorder values were computed for the TRB V-complementarity determining region 3 (CDR3)-J amino acid sequences for all cases. Survival analyses assessed overall survival and disease-specific survival for case sets based on assigning cases to upper or lower 50 th percentile groups, based in turn on intrinsic disorder values. For the phs002683 dataset, intrinsic disorder values were compared between cases representing resistance to immune checkpoint inhibitors (ICIs) and cases representing no observed resistance. The results indicated that the upper 50 th percentile of the range of intrinsic disorder values was linked to better outcomes. This was obtained for two TRB datasets representing different RNA-seq file, recombination read extraction algorithms, and was observed for two different intrinsic disorder models. Furthermore, low minimum various long-3 and various short-long 2 values correlated with ICI treatment resistance. The findings of this study suggest that the diversity of intrinsic disorder values representing TRB V-CDR3-J assemblies may represent a novel prognostic biomarker for metastatic melanoma cases and a potential biomarker for indicating different personalized treatments.

As a highly aggressive skin cancer, melanoma presents substantial clinical challenges stemming from its metastatic potential and therapy resistance, primarily driven by epithelial-mesenchymal transition (EMT). This review examines EMT's central role in melanoma progression. Molecular mechanisms are detailed, encompassing transcription factors (ZEB1, Snail, Twist), signaling pathways (transforming growth factor beta/Smad, Wnt/β-catenin, phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase/extracellular signal-regulated kinase), plus epigenetic and noncoding RNA regulators. Through extracellular matrix remodeling and phenotypic plasticity, EMT potentiates melanoma cell invasion. This facilitation enables key metastatic cascade steps: intravasation and distant colonization. EMT further drives resistance to both targeted therapies (BRAF/MEK inhibitors) and immunotherapies. Mechanisms include T-cell exclusion, PD-L1 upregulation, and immunosuppressive tumor microenvironment remodeling. Tumor progression is amplified via EMT interactions with stromal components, including cancer-associated fibroblasts and immune cells. Prognostically valuable biomarkers are emerging, particularly EMT gene signatures detectable in circulating tumor cells and tissue samples. Preclinical studies suggest therapeutic potential for strategies targeting EMT transcription factors, signaling pathways, and combination approaches. Despite progress, limitations endure: EMT heterogeneity and inadequate preclinical models. Future work will leverage single-cell analysis and spatial transcriptomics to decipher EMT dynamics. Such advances could enable personalized melanoma treatments. EMTs' multifaceted role is underscored herein, along with the urgent requirement for innovative therapeutics to enhance patient outcomes.

To develop a noninvasive diagnostic model integrating deep learning and radiomics for improving the accuracy and clinical utility of early melanoma diagnosis. A total of 350 patients with cutaneous pigmented lesions admitted to our hospital between January 2022 and December 2024 were retrospectively enrolled and randomly divided into a training set ( n  = 245) and a validation set ( n  = 105) in a 7:3 ratio. Complete information were obtained for all patients. Univariate analysis was used to screen factors associated with malignant melanoma. Variables were refined using the least absolute shrinkage and selection operator regression, and independent predictors were identified via multivariate Logistic regression. Random forest (RF), support vector machine (SVM), and K-nearest neighbors (KNN) models were constructed using Python 3.8.5 and the sklearn library. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results from univariate analysis and multivariate logistic analysis showed that lesion diameter, entropy (first-order statistic), long run emphasis, large area emphasis, wavelet contrast, wavelet energy, and the ResNet50-layer49 output were independent risk factors for malignant melanoma (all P  < 0.05). The AUC of the RF model (0.794) was significantly higher than that of the KNN algorithm model (0.755) and the SVM model (0.768), making it the optimal model. The RF model constructed based on deep learning-based radiomics features can be effectively applied to the noninvasive diagnosis of melanoma in patients with cutaneous pigmented lesions. Among these features, entropy (first-order statistic), long-run emphasis, and wavelet contrast are the key predictive indicators.

The treatment of metastatic melanoma has been revolutionized with the introduction of immune checkpoint inhibitors, though approximately 50% of patients will progress at 12 months even with the most robust immunotherapy combinations. As these drugs are now first-line treatment for advanced melanoma, it is imperative to define the role and benefits of multimodal therapy adjunct to systemic therapy. This case describes a patient with v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutant stage IV melanoma who has been treated for over 9 years with a combination of systemic and local therapeutics: anti-Cytotoxic T-lymphocyte associated protein 4 (CTLA4), anti-programmed cell death protein 1 receptor (PD1), and targeted therapies, stereotactic radiosurgery, and multiple metastasectomies. Through multidisciplinary care with the help of genomic analysis, this patent's survival has been extended far past conventional estimates. Molecular profiling revealed an acquired NRAS mutation, which helped explain clinical findings and allowed for a more tailored therapeutic regimen. This report demonstrates that effective surgical resection of nonresponding or progressing lesions can lead to long-term survival even in patients with severe disease burden. Continuous clinical and molecular monitoring can also help shape patients' treatment courses. The effectiveness of multimodal treatment, incorporating local therapies with molecular profiling in conjunction with systemic therapies, should be considered by interdisciplinary care teams to strive for durable survival in patients with historically grim prognoses.

Reexcisions for melanoma do rarely present residual melanoma. To analyze the number of positive margins in reexcisions of in situ and <1 mm melanomas. To see whether the immunohistochemical (IHC) panel (Preferentially expressed antigen of melanoma (PRAME), Sry-related HMg-Box gene 10 (SOX 10), Human melanoma black 45 (HMB45), and Melan A) detected additional cases of melanoma. Three pilot cohorts (retrospective, prospective, and direct safety margins) were analyzed on the persistence of melanoma in reexcisions. Among the 97 cases of the retrospective cohort (27 in situ and 69 invasive melanomas), one residual in situ melanoma was detected in the reexcisions. In the second cohort, among 81 cases (18 in situ and 63 invasive melanomas), two cases (2.5%) presented in situ melanoma. In the group where direct margins were taken ( n  = 21) 2 (9.5%) in situ melanoma were evidenced in the margins. The IHC panel was needed to confirm three additional in situ melanomas in cohort 2. In a total of 178 cases (97 + 81) of reexcision, three and five cases (1.7 and 3.4%) of in situ melanoma were evidenced after H/E and IHC, respectively. These pilot data could question the usefulness of reexcision in <1 mm melanomas, particularly as only cases of in situ melanoma were detected. Larges prospective series would be required to answer this issue.

Artificial intelligence (AI) powered mobile health (mHealth) apps are emerging as vital self-triage tools for skin cancer detection. By utilizing smartphone cameras, these apps analyze skin lesions to assess the risk and provide tailored care recommendations, ranging from self-care guidance to directing users to appropriate healthcare providers. While this positively impacts Sustainable Development Goals 3, the rapid proliferation of these apps introduces significant challenges. A persistent digital divide, stratified by gender, geography, income, and education, limits widespread adoption. It is further exacerbated by varying levels of digital literacy and patient anxieties. The unregulated nature of commercial app stores poses diagnostic risks. At the same time, limited training data for AI models exposes individuals with underrepresented skin types to significant diagnostic errors. Increased self-diagnosis leads to increased downstream care pressures, overwhelming dermatology and pathology services in LMICs. This review highlights the increasing incidence of skin cancer and discusses the risk-benefit profile of mHealth apps in diagnosis. It covers the multifaceted challenges confronting LMICs, including the evolving and fragmented regulatory landscape, while comparing them with those of high-income countries. Finally, we developed a causal loop diagram (CLD) to facilitate informed multistakeholder action for improving public health outcomes through AI-based mHealth apps. The CLD establishes the positive and negative associations of key variables across four pillars: data acquisition and quality, AI model development and validation, user experience and accessibility, and public health impact. We advocate for a multidisciplinary convergence among dermatological experts, AI scientists, app developers, and regulators, fostering international collaboration, knowledge sharing, best practices, and targeted capacity building to ensure equitable and accountable mHealth deployment in LMICs.

Invasive cases of melanoma have increased by 44% annually in the past decade. B-Raf serine-threonine kinase (BRAF)/Mitogen-activated protein kinase kinase (MEK) inhibitors have become the standard of care for stage III/IV BRAF mutant melanoma. Due to limited adverse event (AE) data based on clinical trials, we aimed to describe and compare the AE and outcomes associated with melanoma therapies. A retrospective disproportionality analysis was conducted to assess and compare the trends of AEs associated with BRAF/MEK inhibitors and combinations. The primary data were extracted from the Food and Drug Administration (FDA) Adverse Event Reporting System database from 2012 to 2021. Study drugs included BRAF/MEK inhibitors (dabrafenib, trametinib, vemurafenib, cobimetinib, encorafenib, and binimetinib). A reporting odds ratio (ROR) was calculated for the most common AEs and outcomes reported. We found 195 640 unique AE reports associated with BRAF and MEK inhibitor usage, representing 52 772 patients. The leading AEs associated with BRAFi and MEKi use were as follows: pyrexia, fatigue, nausea, diarrhea, rash, vomiting, and arthralgia. Encorafenib and binimetinib had significant odds for nausea [ROR, 1.91 (1.73-2.11) and ROR, 1.91 (1.73-2.11), respectively]. The incidence of fatigue was highest in the encorafenib [ROR, 1.71 (1.54-1.90)], binimetinib [ROR, 1.74 (1.57-1.94)], and vemurafenib [ROR, 1.27 (1.14-1.27)] groups. Cobimetinib had significantly increased odds for developing a disability [ROR, 4.95 (4.28-5.74)], having a hospitalization [ROR, 2.08 (1.99-2.17)], and experiencing a life-threatening event [ROR, 1.78 (1.55-2.03)]. AE reports associated with melanoma therapies are sizable and significant. Healthcare professionals should be aware of the AE profiles attributable to the melanoma treatment and management.

Uveal melanoma is a rare malignancy with a strong propensity for late metastases, most commonly affecting the liver. Pulmonary metastases are less frequent and can manifest years or even decades after the primary diagnosis. This study presents three cases of pulmonary metastases secondary to uveal melanoma, highlighting clinical presentations, treatment strategies, and outcomes following surgical intervention. A retrospective analysis of 132 patients diagnosed with uveal melanoma between 2009 and 2022 at one institution was conducted. Clinical and pathological data were reviewed to assess primary tumor characteristics, metastatic patterns, treatment approaches, and patient outcomes. Three patients were identified with pulmonary metastases, diagnosed at least a decade after primary tumor treatment. The metastatic presentation varied, with one patient exhibiting bilateral multiple nodules, while the other two had solitary pulmonary lesions. All patients underwent video-assisted thoracoscopic surgery wedge resection, confirming metastatic melanoma. Two patients remained disease-free following resection, while one developed systemic progression with small bowel metastases, ultimately leading to fatal complications. Surgical resection of isolated pulmonary metastases from uveal melanoma may offer clinical benefit in highly selected patients. While not a standard treatment modality, pulmonary metastasectomy may be appropriate in selected patients and can be considered within the context of a multidisciplinary evaluation.

Uveal melanoma is the most common intraocular malignancy in adults. Prognostic markers such as monosomy 3 and chromosome 8q gain are well validated in Western cohorts but remain unproven in Indian patients. We retrospectively analysed 30 tumours (17 metastatic, 13 nonmetastatic) using the OncoScan FFPE Assay Kit. Loss of chromosome 6q was strongly associated with metastasis (odds ratios, 23.2; 95% confidence intervals, 2.5-214; P < 0.001), compared to monosomy 3 and 8q gain. Multivariate analysis confirmed 6q loss as the dominant independent predictor. These findings support population-specific prognostic models and highlight the clinical value of integrating 6q status into risk assessment.

Inflammation, well-known as one of the hallmarks of cancer, has been demonstrated to have a key role in the incidence and growth of different tumors. However, its role as a prognostic factor for melanoma has not yet been clarified. Our study aimed to evaluate the correlation of neutrophil to lymphocyte ratio (NLR), platelet to monocyte ratio (PMR), systemic inflammation index (SII), and aggregate index of systemic inflammation (AISI) with clinical stages of disease, to define whether higher values of these markers correlate with a more aggressive disease. We retrospectively analyzed NLR, PMR, SII, and AISI in a total of 129 newly diagnosed melanoma patients. All values were calculated using the complete blood count data. Higher NLR was associated with advanced stages ( P  < 0.001). Mean NLR among patients with early stage disease (IB and IIA) was 2.01, while the mean NLR for patients with advanced stage disease (from stage IIB to IV) was 3.22. Mean PMR among patients with early stage disease (IB and IIA) was 520, while the mean PMR for patients with advanced stage disease was 479 ( P  = 0.049). Mean AISI in the early stage was 247 and 482 in advanced stages ( P  < 0.001). Mean SII was 480 in the early stage and 747 in advanced stages ( P  = 0.004). Our data confirmed the association between NLR and newly reported the association of PMR, AISI, and SII with high-risk and aggressive melanoma. Further investigations are required to define a meaningful prognostic system for patients with advanced melanoma. This could help classify patients with advanced stages of disease, demanding a short follow-up.

To explore the functional role of thrombospondin 2 (THBS2) in the metastasis of skin cutaneous melanoma (SKCM), with a focus on its regulation of angiogenesis and extracellular matrix (ECM) remodeling. THBS2 expression was assessed in normal melanocytes and SKCM cell lines with varying metastatic potential. Functional analyses were conducted after THBS2 knockdown in A375 cells and overexpression in G-361 cells. Effects on migration, invasion, endothelial tube formation, and angiogenesis- and ECM-related factors were evaluated. Tumor IMmune Estimation Resource database was used for correlation analyses in SKCM samples. A liver metastasis model was established by intrasplenic injection of B16-F10 cells into Thbs2 knockout and wild-type mice, followed by quantification of hepatic metastases and molecular analysis of peritumoral liver tissue. THBS2 was highly expressed in invasive melanoma cell lines and was positively associated with VEGFA, PECAM1, and MMPs in both databases and experimental models. Knockdown of THBS2 significantly suppressed VEGFA, PECAM1, FGF2, FLT1, MMP2, MMP9, and ECM components (LAMA4, COL1A1, and COL4A1) at mRNA and protein levels, inhibited melanoma cell migration and invasion, and reduced tube formation in human umbilical vein endothelial cells. Overexpression had opposite effects. In vivo , Thbs2 knockout mice exhibited significantly fewer hepatic metastases and reduced metastatic area compared with wild-type controls. Expression of Lama4, Pecam1, Vegfa, Mmp2, and Mmp9 was markedly lower in peritumoral liver tissue of knockout mice. THBS2 promotes SKCM metastasis by enhancing angiogenesis and ECM remodeling. Targeting THBS2 may represent a promising strategy for inhibiting melanoma progression and distant organ colonization.

This case report and literature review detail and contextualise the finding of a positive sentinel node in the contralateral axilla of a 69-year-old male with cutaneous malignant melanoma of the left chest wall. Excision biopsy confirmed nodular melanoma (Breslow thickness 6.6 mm; mitotic index 11; no ulceration or microsatellites; completely excised; pT4a). Preoperative lymphoscintigraphy identified the sentinel node in the right axilla. The patient underwent wide local excision with 2-cm margins and a sentinel lymph node biopsy, which showed no spread of disease. This was followed by six cycles of adjuvant pembrolizumab with surveillance scans remaining clear. Literature review identified 22 cases of anterior chest wall melanoma (n = 4) or breast carcinoma (n = 18) with contralateral drainage (12 case reports, two case series, and eight retrospective studies). Only one previous chest wall melanoma case with contralateral drainage was identified, but details were not reported. Thus, we present the first documented case of anterior chest wall melanoma with a contralateral sentinel node, and emphasise the importance of thorough evaluation of suspicious lesions for unexpected drainage patterns.