Apoptosis is an important co-factor in the pathogenesis of a plethora of malignancies. Enhanced c-myc activation can result either in proliferation or apoptosis. Coexpression with antiapoptotic bcl-2, which abrogates the apoptotic function of c-myc might lead to an enormous growth advantage of cells. In order to elucidate the role of c-myc and bcl-2 as well as the coexpression of both genes in human melanoma, their expression was studied in four samples of normal skin (SK), 15 surgical margins (SM), 20 benign melanocytic nevi (MN), 20 primary melanomas (MM), and 30 melanoma metastases (MMET) by RT-PCR. These results were compared with immunohistochemistry (IH) in 7 SK, 7 SM, 26 MN, 50 MM, and 34 MMET. Similar results were found with both methods. However, MMET expressed c-myc (PCR 28/30, IH 23/34) as well as bcl-2 (PCR 27/30, IH 24/34) more frequently. Primary melanomas showed a similar expression pattern as SM and nevi. Moreover, in contrast to SK, SM, MN, and MM coexpression of bcl-2 and c-myc was found more frequently in MMET (PCR 25/30, p < 0.01, IH 19/34, p < 0.01). These results indicate that coexpression of c-myc and bcl-2 appears to be associated with advanced melanoma and contributes to the malignant phenotype.