Mutations in the p53 tumor suppressor gene are a common finding in many human malignancies. These mutations have been shown to inactivate the p53 protein and sometimes confer an oncogenic potential to the mutated gene. Type and pattern of p53 mutations may give clues to the tumor etiology, for example, ultraviolet-induced CC → TT and C → T transitions. Genomic DNA of 16 primary cutaneous melanomas of the superficial and nodular subtype and six melanoma metastases were screened for the presence of mutations in exons 5 to 8 of the p53 tumor suppressor gene, using the polymerase chain reaction and single-strand conformation polymorphism analysis, followed by direct DNA sequencing. We detected no mutations in any of the primary and metastatic melanomas in exons 5 to 8 of the p53 tumor suppressor gene. This indicates that, in contrast to skin carcinomas, p53 mutations are not operative in the evolution of human melanoma.