Activation of the Ha-ras oncogene by point mutations has been suggested to play a role in animal skin carcinogenesis models. In this study, we investigated the significance of the Ha-ras mutations in human epidermal tumors. DNAs from paraffin-embedded tissues of benign and malignant human epidermal tumors (27 samples from 25 patients) were prepared and examined for point mutations of codons 12, 13 and 61 of Ha-ras gene by polymerase chain reaction and oligonucleotide hybridization. Only one sample of basal cell carcinoma and one sample of keratoacanthoma were found to carry an A to T transversion at the second position of codon 61. This low incidence of Ha-ras mutations suggests that the mutational activation of the gene may not be primarily involved in human epidermal tumorigenesis.