OBJECTIVES. The aim of the study was to look into the number of melanomas diagnosed over a four-year period, examine the incidence of melanoma depending on classification according to Breslow and Clark, and compare special histochemical Fontana-Masson staining and immunohistochemical methods in the diagnosis of melanoma. STUDY DESIGN. Cross-sectional study with historical data. PARTICIPANTS AND METHODS. The study covers 120 primary melanomas diagnosed at the Clinical Department of Pathology and Forensic Medicine, Clinical Hospital Center Osijek over a four-year period from 2016 to 2020. Tissue samples were stained by the standard Hemalaun-Eosin staining method and the Fontana-Masson special histological staining method. In addition to histological processing, immunohistochemical analysis for Melan A, HMB-45 and Ki-67 was performed. Sakura Tissue-Tek Prisma Plus Automated Slide Stainer and Sakura Tissue-Tek Film Automated Coverslipper were used for the hemalaun-eosin staining technique. Roche's Ventana BenchMark Ultra was used for immunohistochemical analysis. RESULTS. The majority of respondents were men (53 %). Most malignant melanomas affect the population aged 60 to 69 (28 %). Regarding localization, most melanomas is localized on the skin (97.5 %). According to the Clark and Breslow classification, most common melanoma stanges were Clark IV (37.5 %) and Breslow V (35 %). Most respondents had Ki-67 values up to 10 % (36 %), and in the range of 21 to 50% (36 %). Most tumors (98.7 %) are positive in immunohistochemical analysis. CONCLUSION. The reason for the increased incidence of malignant melanoma is the constant skin exposure to harmful environmental factors, especially harmful UV radiation. Of great importance is the immunohistochemical analysis of tumor tissue and Clark and Breslow grading with TNM classification as a prognostic factor.