Benefit-risk assessment of systemic treatment in psoriasis is a dynamic process. Long-term safety of psoriasis therapies has been questioned, with the spectrum of systemic immunosuppression potentially leading to increased cancer risk. In this issue, Brauchli et al. report on a population-based analysis of cancer risk in a large cohort of psoriasis patients, most of whom had not been treated with systemic agents. The study prepares the ground for future prospective long-term cohort studies in psoriasis patients treated with systemic therapies, including biological agents.