A large number of benign melanocytic nevi is the major risk factor for malignant melanoma (MM). In a multicenter case-control study, the number of common (CN) and clinically atypical (AN) nevi were counted separately at individual sites in 278 melanoma patients and 278 age- and gender-matched non-melanoma controls. Relative risk (RR) adjusted for age and sex was calculated. In men as well as women, the number of CN on the legs was the best predictor of overall melanoma risk. In men, RR for developing MM when > or = 1 AN were present on the trunk was 4-fold (vs. none). In women, presence of AN on the arms increased RR 9.5-fold. For men and women combined, after adjusting for age and gender, the RR for developing MM on the trunk and on the legs was best predicted by counts of CN at the respective body region. However, high counts of CN on the arms were associated with high melanoma risk on the legs (somewhat lower on the trunk). For AN, no site-specificity of melanoma risk was found. Our data suggest that nevus counts of the legs are the best predictor of overall melanoma risk if total body nevus counts are not feasible. Although high counts of CN on the trunk and legs are associated with a higher risk of developing MM at the respective site than at another site, our data do not unequivocally support a direct site-specific melanoma risk.