Psoralen+ultraviolet A-treated psoriasis patients are at increased risk for nonmelanoma skin cancer. To assess the persistence of cancer risk among patients who have discontinued psoralen+ultraviolet A and the risk of a first tumor with the passage of time, we prospectively studied the incidence in a cohort of 1,380 psoriasis patients treated with psoralen+ultraviolet A. We observed a total of 27,840 person-years of which 59.4% were considered years without psoralen+ultraviolet. No significant decrease in risk was noted during the first 15 years after psoralen+ultraviolet A was discontinued. Subsequently, the risk of squamous cell carcinoma was reduced (incidence rate ratio=0.79; 95%CI=0.62, 1.01 on treatment vs >15 years off). After 25 years, about 7% of patients with < or =200 psoralen+ultraviolet A treatments and more than half of the patients with > or =400 treatments develop at least one squamous cell carcinoma. After 25 years, almost one third of the patients exposed to > or =200 treatments developed at least one basal cell carcinoma. In conclusion, substantial exposure to psoralen+ultraviolet A dramatically increases the risk of nonmelanoma skin cancer and prior exposure to psoralen+ultraviolet A remains an important issue in the management of patients because the cancer risk associated with psoralen+ultraviolet A is persistent.