Moderate to severe psoriasis often requires treatment with systemic agents, many of which have immunosuppressive properties and could increase cancer risk, including nonmelanoma skin cancer (NMSC). We sought to estimate the overall malignancy rate (excluding NMSC) and NMSC rate among 5889 patients with systemically treated psoriasis. We identified a cohort of adult Kaiser Permanente Northern California health plan members with psoriasis diagnosed from 1998 to 2011 and treated with at least 1 systemic antipsoriatic agent and categorized them into ever-biologic or nonbiologic users. Malignancy rates were calculated per 1000 person-years of follow-up with 95% confidence intervals (CI). Crude and confounder-adjusted hazard ratios (aHRs) were calculated using Cox regression. Most biologic-exposed members were treated with TNF-alfa inhibitors (n = 2214, 97%). Overall incident cancer rates were comparable between ever-biologic as compared to nonbiologic users (aHR 0.86, 95% CI 0.66-1.13). NMSC rates were 42% higher among individuals ever exposed to a biologic (aHR 1.42, 95% CI 1.12-1.80), largely driven by increased cutaneous squamous cell carcinoma risk (aHR 1.81, 95% CI 1.23-2.67). No information was available on disease severity. We found increased incidence of cutaneous squamous cell carcinoma among patients with systemically treated psoriasis who were ever exposed to biologics, the majority of which were TNF-alfa inhibitors. Increased skin cancer surveillance in this population may be warranted.