Epidemiological studies on the relation between selenium and human cancer have yielded strongly conflicting results. Prompted by the observation of a positive association between selenium intake and site-specific cancers, including melanoma, in a large cohort of nurses, we studied the 11-year melanoma incidence in an Italian cohort that consumed unusually high levels of inorganic selenium in tap water from 1975 to 1985. The setting was Reggio Emilia, an Italian municipality that provided a natural experiment relating to intake of high levels of inorganic selenium. We identified 2,065 individuals with high selenium exposure, who contributed a total of 20,179 person-years of follow-up, and we compared their experience with the 1,384,386 person-years of follow-up in the remaining population of Reggio Emilia. We included all cases of pathologically confirmed malignant melanoma, including intraocular melanoma, identified from the Reggio Emilia Hospital, the Bologna regional registry of hospital discharges, and the Milan National Cancer Institute. Eight cases of malignant melanoma occurred in the exposed cohort during the follow-up. Melanoma incidence was 3.9 times greater in the exposed than in the unexposed cohort (95% exact confidence limits, 1.8-7.4).