Background Genetic findings suggesting a lower susceptibility to melanoma in patients with vitiligo are supported by recent clinical studies. Nonmelanoma skin cancer (NMSC) has also been studied, but mainly in small samples, and with conflicting results. Objective We sought to study the relative risk (RR) of melanoma and NMSC in patients with vitiligo compared with that in patients seen for vascular surgery. Methods The frequency of melanoma and NMSC was compared between patients with vitiligo and patients seen for vascular surgery. Occurrence of skin cancer was compared by computing RR and modeled using multiple logistic regression. Results Overall, the crude RR for melanoma was 0.24 (95% confidence interval CI 0.13-0.45) in patients with vitiligo compared with those with a nondermatologic condition (occurrence 1.1‰, 95% CI 0.5‰-2.0‰ in patients with vitiligo and occurrence 4.5‰, 95% CI 3.8‰-5.4‰ in the control cohort). The crude RR for NMSC was 0.19 (95% CI 0.14-0.17) and the occurrence was 3.8‰ (95% CI 2.7‰-5.2‰) among patients with vitiligo and 19.6‰ (95% CI 18.0‰-21.4‰) in control subjects. Patients with vitiligo who underwent phototherapy had a markedly higher risk of both cancers. Conclusions In our large study, patients with vitiligo have a decreased risk of developing skin neoplasms, even considering that a larger proportion in this patient group is exposed to higher levels of ultraviolet radiation.