Polymorphisms of the cyclin-dependent kinase inhibitor gene p21 have recently been reported to be associated with several human cancers. To determine whether the polymorphisms are also associated with human skin cancers, we investigated the p21 polymorphisms in 165 healthy Japanese and 113 Japanese with malignant skin tumors: 30 squamous cell carcinoma, 20 malignant melanoma, 33 basal cell carcinoma, and 30 Bowen's disease. The p21 polymorphisms were characterized by single base substitutions in the following two sites: the last nucleotide of codon 31 of exon 2 and the site 20 nucleotides downstream from the 3' end of exon 3. The two polymorphic sites were reported to be firmly linked to each other. We have shown that the two sites were firmly linked to each other also in Japanese and that no associations of the polymorphisms with the skin cancers in Japanese were detected by statistical analysis. Although the p21 polymorphisms were found not to be involved with skin carcinogenesis, ethnic differences of the allele frequency distribution must be taken into account in studying the role of the p21 polymorphism in carcinogenesis.