Melanoma is a malignant tumor of melanocytes that arises predominantly in the skin but can also develop from melanocytes in the eye. Usually it is diagnosed in the middle-aged population, but it also occurs in younger people with an increase in the number of patients every year. Numerous exogenus (mostly UVB radiation) and endogenous factors (number of moles, skin type and pigmentation, familial tendency to melanoma), influence the incidence of malignant melanoma. The diagnosis of melanoma is established by using numerous diagnostic procedures. The anamnesis collects data on the changes of the mole and on genetic trait for melanoma. Clinical status and dermatoscopy findings raise a suspicion of melanoma, and pathohistological analysis confirms the diagnosis. The determination of the clinical stage of melanoma is performed using the American Joint Committee on Cancer (AJCC) guidelines, which include the T, N and M categories (T- primary tumor characteristics, N- regional lymph nodes status, M- presence of distant metastases). In the pathohistological examination of melanoma, tumor thickness is a major prognostic factor and two tumor-based classifications, Breslow's classification and the classification according to Clark are the most commonly applied. The diagnosis of melanoma metastatic to regional lymph nodes is performed by clinical and ultrasonic examination of the lymph nodes regions adjacent to the tumor area, and in the case of a suspicious finding, fine-needle aspiration (FNA) cytology is used. Sometimes, melanoma is diagnosed in metastasis as the primary manifestation of the tumor, most commonly by FNA cytology of an enlarged lymph node. The appearance of melanoma cells in cytological smears is highly variable. Malignant cells may show marked anisocytosis and anysonucleosis, nuclear pleomorphysm, binucleation or multinucleation, intranuclear inclusions, and may have the gray-black pigment melanin in the cytoplasm. The difficulties in cytological diagnosis of melanoma, especially when FNA of a metastatic lesion represents the first encounter with the patient, are coming from that broad spectrum of cytomorphological characteristics that may be misleading. The cytological picture can be very clear if malignant cells contain melanin, but if not, the cytomorphological diagnosis of melanoma may be impossible. Melanoma cells can resemble different tumors and can be found in all parts of the body. In such cases, immunocytochemical analysis is applied on cytological smears, and that enables the recognition of melanoma. From the samples obtained by the FNA method, cell-blocks can be made, thus making the cytological specimen more suitable for immunohistochemical analysis. Melanoma cells are most commonly vimentin, S-100, melan A and HMB-45 positive. For a number of years, the important part of the operative melanoma treatment was an intraoperative sentinel lymph node (SLN) analysis. This procedure involves identification, extirpation and intraoperative cytological and/or pathohistological analysis of SLN on frozen sections. According to the latest NCCN 2018 guidelines, intraoperative SLN analysis is no longer performed. SLNs are still labeled and removed, but the sample is analyzed on standard paraffin blocks. In addition to standard tissue diagnostic assays in melanoma, molecular testing is also performed, primarily the detection of BRAF V600E mutation, due to the availability of targeted therapy. This examination is performed on the primary tumor, but also on metastatic lesions and recurrent tumors, and can also be performed on cytological samples. The follow-up of melanoma patients is carried out throughout their lives, especially during the first 5 years after diagnosis, because of a high recurrence rate. Cytology also plays an important role in the early detection of metastatic lesions, which may occur even after many years and in almost any part of the body. Cytological analysis does not apply to the diagnosis of primary pigmented skin lesions, but is an indispensable diagnostic method for the early detection of metastatic lesions and recurrent melanoma.