The oncogenic transformation of epidermal melanocytes produces primary cutaneous melanoma. In this article, previously published cytogenetic, biochemical, molecular biology, and cell biology studies of cutaneous melanoma oncogenesis are reviewed. A variety of laboratory animal models have been developed for studies of the induction of melanoma, including mice, the laboratory opossum Monodelphis domestica, Sinclair swine, and Xiphophorus fish. Some of the advantages and disadvantages of these animal models are presented for comparison to human melanoma. Cytogenetic and loss of heterozygosity studies over the past decade have demonstrated that human metastatic melanomas contain numerous chromosomal abnormalities, and that normal melanocytes have putative tumor suppressor genes that are presumably deleted or inactivated in transformed melanocytes to yield malignant melanoma cells. The status of research efforts to identify the putative tumor suppressor genes of human chromosomes 1p, 6q, and 9p, implicated in sporadic and familial melanoma, is presented. Furthermore, the roles of ultraviolet radiation, genetic susceptibility, dominant oncogenes, growth factors, the p53 gene, antioxidant enzymes, and DNA tumor viruses in the formation of cutaneous primary melanoma are discussed.