INTRODUCTION: Melanomas originate from melanocytes and can be fatal. Surgical excision is primary, but due to potential rapid metastases, additional therapies are crucial. Our study aimed to assess Lymphocyte-activation gene 3 (LAG-3) and T-cell immunoglobulin and mucin domain 3 (TIM-3) expression in melanoma, exploring their relationships with survival and clinicopathological data. METHODS: The study included 64 melanoma skin excision samples examined at the Pathology Department of Saglik Bilimleri University Prof. Dr. Cemil Tascioglu City Hospital between 2017-2023. LAG-3 and TIM-3 immunohistochemical studies were conducted by two pathologists to assess their expression rates and intensities. The study investigated correlations between these markers and epidemiological, clinical, and histopathological features of the cases. Statistical analysis was performed using SPSS 27, with significance levels set at p<
0.05. RESULTS: There was a significant association between LAG-3 and TIM-3 expressions (p: 0.002). LAG-3 expression correlated significantly with progression free survival (PFS) and overall survival (OS) rates (p: 0.020
p: 0.023). However, TIM-3 expression did not show significant correlations with PFS and OS times (p: 0.726
p: 0.903). Both LAG-3 and TIM-3 expressions were elevated in deceased patients (p: 0.002
p: 0.042). LAG-3 positivity was identified as an independent risk factor for OS, regardless of disease stage (p: 0.008). CONCLUSIONS: Research on immune checkpoint inhibitors has intensified in recent years. The expression of LAG-3 and TIM-3 is associated with poor prognosis in melanomas. Combined treatments targeting these markers may be beneficial in the treatment of this disease.