Squamous-cell cancer occurs only rarely on the male genitalia. In a 12.3-year prospective study of 892 men in a cohort of patients with psoriasis who had been treated with oral methoxsalen (8-methoxypsoralen) and ultraviolet A photochemotherapy (PUVA), we identified 14 patients (1.6 percent) with 30 genital neoplasms. The standard morbidity ratio (which was used as a measure of the risk of a genital neoplasm) comparing morbidity among patients treated with PUVA with that expected on the basis of population incidence data was 95.7 (95 percent confidence interval, 43.8 to 181.8) for invasive squamous-cell carcinoma of the penis and scrotum, and 58.8 (26.9 to 111.7) for invasive and in situ penile tumors. In patients exposed to high levels of PUVA, the incidence of invasive squamous-cell carcinoma was 286 times that in the general population and 16.3 times that in patients exposed to low levels (P less than 0.001 for both comparisons). After controlling for the level of exposure to PUVA, we found that patients exposed to high levels of ultraviolet B radiation had a risk of genital tumors 4.6 times higher than that in other patients (95 percent confidence interval, 1.4 to 15.1). The strongly dose-dependent increase in the risk of genital tumors associated with exposure to PUVA and ultraviolet B radiation that we observed makes it prudent for men to use genital protection whenever they are exposed to PUVA or other forms of ultraviolet radiation for therapeutic, recreational, or cosmetic reasons.