BACKGROUND: Antioxidant nutrients can help prevent skin damage caused by ultraviolet radiation from sunlight, but it is not clear whether serum concentrations of such nutrients influence skin cancer risk. METHODS: We carried out a prospective study of the associations between serum concentrations of antioxidant nutrients and incidence (person-based and tumor-based) of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin among a random subsample of 485 adults from an Australian community. Participants were divided into thirds, ranked according to their serum concentrations of carotenoids, alpha-tocopherol, and selenium measured in 1996 and were monitored for incident, histologically confirmed BCC and SCC tumors until 2004. RESULTS: Although there were no associations between baseline serum carotenoids or alpha-tocopherol concentrations and incidence of BCC or SCC, baseline serum selenium concentrations showed strong inverse associations with both BCC and SCC tumor incidence. Compared with participants with lowest selenium concentrations at baseline (0.4-1.0 micromol/L), those with the highest serum selenium concentrations (1.3-2.8 micromol/L) had a decreased incidence of BCC tumors (multivariate relative risk, 0.43; 95% confidence interval, 0.21-0.86; P(trend) = 0.02) and SCC tumors (multivariate relative risk, 0.36; 95% confidence interval, 0.15-0.82; P(trend) = 0.02). CONCLUSION: Relatively high serum selenium concentrations are associated with an approximately 60% decrease in subsequent tumor incidence of both BCC and SCC, whereas serum concentrations of carotenoids or alpha-tocopherol are not associated with later skin cancer incidence. A possible U-shaped association between serum selenium concentrations and SCC of the skin needs confirmation.