The frequency of integration with human papillomavirus (HPV) and its genotypes in Japanese penile cancer was examined with relation to p53 gene mutations using polymerase chain reaction amplification. Tissues were obtained from 13 patients (eight from freshly frozen and five from paraffin-embedded samples). HPV DNA was detected in seven out of the 13 (54%), and their genotypes were type 16 in four, type 31 in one and type 33 in two cases. Neither HPV-detected nor -undetected tissues showed mutated alterations in exons 4-9 of p53 genes. The results suggest HPV to be, at least to some extent, involved in the oncogenesis of penile cancer, and that p53 gene mutations may not correlate with the development of penile cancer.