The incidence rate of clinically apparent prostatic carcinoma is 8-fold higher in the United States than in Japan, while the prevalence of latent prostatic carcinoma, a presumed precursor to clinical carcinoma, is similar in the two countries. The purpose of this study was to investigate the hypothesis that this profound difference in incidence rates of clinical carcinoma reflects distinct profiles of molecular genetic alterations in the latent precursor lesions that occur in the two countries. A significant fraction of latent carcinomas from Japanese men were found to contain inactivating mutations of the androgen receptor gene, while no such mutations were found in latent carcinomas from American men. No mutations were found in clinical carcinomas from either country. These data offer a potential molecular genetic explanation that may partially account for the distinct prostatic carcinoma incidence rates in these two populations.