BACKGROUND: Determination of the cytogenetic origin and morphological type of metastatic or primary tumor determines the prescription of therapy and affects the efficiency of patient’s treatment. Currently, a number of publications evaluate the potential of cytological diagnostics of melanoma. AIM: To evaluate the significance of diagnosing metastatic melanoma by fine-needle aspiration biopsy and primary melanoma by using the skin and mucosa imprints. METHODS: In a retrospective study, a comparative analysis of cytological melanoma samples, in comparison with clinical and anamnestic information and the results of histological, immunohistochemical, and molecular genetic studies, was carried out. Information about 109 patients from the cancer registry of the Altai Regional Oncology Dispensary (Barnaul, Russia) for 2022 was used in the study. Traditional and liquid-based methods for preparing samples were used. The samples were stained using Pappenheim and Papanicolaou methods. In some observations, cytological material was used for molecular genetic studies. Using the cancer registry data of the dispensary, the results of histological and of molecular genetic studies, and a final conclusion was given about each patient. RESULTS: Fine-needle aspiration biopsy was carried out in 80 patients. Tumor smears were obtained from 29 patients. The cytological diagnose “melanoma” was consistent with the data of histological and immunohistochemical studies (p 0.001) for all 109 patients. Melanoma was diagnosed for the first time in 66 (60.5%) patients. In other cases, the process of progression was noted within the period from one year to 20 years. Epidermal melanoma was noted in 101 (92.7%) cases, including 9 patients with acral melanoma, and 2 cases with localization on the vulva. Melanomas of mucosa were found in 5 cases (4.5%): in the rectum and anal canal, vagina, and in 2 cases on the hard palate. Non-epidermal (uveal) melanomas metastases were diagnosed in liver by fine-needle aspiration biopsy in 3 patients (2.8%). Based on the cellular composition, epithelioid cell melanoma was determined in 81 (74.3%) patients, mixed cell in 14 (12.8%) cases, spindle cell in 9 (8.2%), pigmentless in 2 (1.8%) cases and nevoid melanoma in 1 (0.9%) case. The mutation status was determined in 96 patients (88.1%). Of these, in 8 patients it was determined using cytological material. In epidermal melanomas, mutations in codon 600 of exon 15 of the BRAF gene were found in 43 (44.8%) patients, including 2 cases of acral melanoma. Mutations V600K, V600E/Ec were found in one patient each. In mucousal melanomas: Q61R mutation was found in exon 3 of the NRAS gene (vaginal melanoma), G12C mutation was identified in exon 2 of the NRAS gene (anal canal melanoma). In uveal melanomas, the assessed mutations were absent (it is necessary to determine mutation is GNAQ11 and BAP1 genes). CONCLUSION: Cytological diagnosis of melanoma by fine-needle aspiration biopsies and imprints from the tumor mass is a highly informative method that allows diagnosing melanoma and verifying the tumor subtype. The obtained results indicate tumor heterogeneity and differences in mutational status depending on the location of melanomas. The molecular classification of melanoma is important when choosing individualized therapy.