To test the validity of the common hypothesis that patients with psoriasis have an inherently lower susceptibility to cancer, we prospectively studied 1367 patients with severe psoriasis who enrolled in a clinical trial of oral methoxsalen photochemotherapy for treatment of psoriasis for an average of 3.2 yr. The incidence of non-cutaneous cancers and the number of deaths from such cancers were slightly but not significantly higher than that expected for the general population (relative risk = 1.1; standard mortality ratio = 1.3). Among 318 patients (23%) in this cohort who were over 35 yr of age and who lacked appreciable exposure to suspected cutaneous carcinogens, the observed incidence for cutaneous carcinoma was 1.4 times that expected, based on rates for the general population (90% confidence interval = .8 to 2.7). These data suggest that patients with psoriasis have a risk of systemic and cutaneous cancer that is comparable to the risk for the general population.