Nodular melanoma is the most aggressive variant of malignant melanoma which represents about 20-30% of all melanoma cases. In order to obtain better insight into the genetic background of this specific type of melanoma, we aimed to analyze the frequency of CDKN2A deletion and C-MYC increased copy number changes. The impact of these aberrations on the metastatic potential and patient's survival was considered. Fluorescent in situ hybridization with C-MYC and CDKN2A specific fluorescent-labelled probes were applied on isolated nuclei from 49 paraffin-embedded primary nodular melanomas. The study showed CDKN2A deletion in 73.47% of the analyzed cases of which 22.45% additionally displayed C-MYC increased copy numbers. CDKN2A deletions were observed in melanomas with Breslow thickness ≤1.0 and ≥1.1 mm whereas C-MYC gain in combination with CDKN2A deletion appeared only in tumors ≥1.1 mm. The combined C-MYC and CDKN2A aberrations were found predominantly in the non-metastasizing group of primary NM. The survival analysis furthermore demonstrated that patients with combined CDKN2A and C-MYC aberrations have a significantly better prognosis than carriers of CDKN2A deletion only (p = 0. 0218). We conclude that C-MYC increased copy number changes on the background of CDKN2A deletions seem to be related to a low metastatic potential and better patients' outcome in primary nodular melanomas.