Objective: Distinction between benign and malignant melanocytic lesions commonly represents a big challenge for the pathologist. In this case it appears as a useful auxiliary method of fluorescence in situ hybridization (FISH). The aim of this study was by using fluorescently labeled probes detection of numerical changes occurring in malignant melanoma and thus supply or confirm the diagnosis. Method: The retrospective study included 14 samples tissue with an established histological diagnosis (6x malignant melanoma, benign melanocytic lesions 8x). For detection was used probe Vysis LSI RREB1/LSI Myb/LSI CCND1/ CEP6 (Abbott Molecular, USA), Olympus AX70 fluorescent microscope (immersion lens 1000x). In the area of the tumor were calculated signals of individual probes and evaluated according to the manufacturer's instructions. Results: Evaluable results were obtained in 10/14 Cases (71 %) of the melanomas were 4 and 6 benign melanocytic lesions. In all four cases of malignant melanoma have been burdened with genetic changes, mainly in the CCND1 (in 55 %) gene amplification and PREB1 (in 40 %) and MYB (in 5 %). In contrast, for all 8 benign melanocytic been demonstrated normal findings. Conclusion: DNA abnormalities detected by FISH occurr in the vast majority of malignant melanomas but are not seen in benign nevi. This fact make the FISH test an important extra step in the differential diagnosis melanocytic lesions with ambiguous or borderline histological findings. 