Cutaneous melanoma is becoming increasingly common. Genetic and environmental factors are thought to play a role in its pathogenesis. We have previously shown that normal human melanocytes strongly express the oncoprotein, Bcl-2. To determine the role of Bcl-2 in melanocytic tumors, we studied human benign nevi and melanomas for expression of Bcl-2 protein using immunohistochemistry. Our results show that benign melanocytes from 3 of 4 normal skin biopsies and 5 of 7 common acquired nevi strongly express Bcl-2. Conversely, only 3 of 23 primary cutaneous melanomas and 3 of 9 metastatic melanomas showed strong staining in comparison with melanocytes from normal skin and common acquired nevi (chi 2, P = 0.0021). Interestingly, 0 of 6 dysplastic nevi, a precursor of melanoma, demonstrated strong staining as compared with melanocytes and nevi (8 of 11; chi 2, P = 0.02), but similar expression to that of melanoma (6 of 32; chi 2, P = 0.6). We conclude that Bcl-2 expression decreases in malignant melanoma and suggest that this may be related to the autonomous growth characteristics of malignant melanoma.