Psoralen + ultraviolet A-treated psoriasis patients are at increased risk for squamous cell carcinomas and basal cell carcinomas; however, the incidence and risk factors associated with second squamous cell carcinomas and basal cell carcinomas in this population are not well qualified. Incidence and risk factors for second squamous cell carcinomas and basal cell carcinomas were studied in a cohort of 1380 psoralen + ultraviolet A-treated psoriasis patients prospectively followed for over 20 y; 264 had a squamous cell carcinoma and 258 a basal cell carcinoma after beginning psoralen + ultraviolet A therapy. After a first squamous cell carcinoma, the risk of a second squamous cell carcinoma was 26% at 1 y, 62% at 5 y, and 75% at 10 y. Risk increased with high psoralen + ultraviolet A exposure prior to the first squamous cell carcinoma (hazard ratio 3.32, 95% confidence interval 1.53, 7.18). Higher rates of post-first squamous cell carcinoma psoralen + ultraviolet A treatment also were associated with greater risk (hazard ratio 1.56 for every additional 10 treatments per year for patients with low pre-first squamous cell carcinoma psoralen + ultraviolet A exposure, 95% confidence interval 1.35, 1.81). Patients exposed to high levels of tar and/or ultraviolet B before a first squamous cell carcinoma were also at higher risk (hazard ratio 1.72, 95% confidence interval 1.14-2.60). Risk of a second basal cell carcinoma was 21% at 1 y, 49% at 5 y, and 61% at 10 y. There was some evidence that high exposure to psoralen + ultraviolet A before a first basal cell carcinoma was associated with increased risk of second basal cell carcinoma (hazard ratio 1.45, 95% confidence interval 0.97-2.17). Higher post-first tumor psoralen + ultraviolet A treatment rates also increased risk (hazard ratio 1.24 for every additional 10 treatments per year, 95% confidence interval 1.06-1.47). Psoralen + ultraviolet A-treated psoriasis patients appear to have a greatly increased incidence of second squamous cell carcinoma compared with the general population. Patients who develop a squamous cell carcinoma after starting psoralen + ultraviolet A therapy should be closely monitored for a subsequent squamous cell carcinoma.