A role of cadmium exposure in prostate cancer etiology has been suggested by epidemiologic and laboratory studies, but conclusive evidence on this topic is still lacking. We investigated the relation between cadmium exposure, estimated by determining toenails cadmium levels, and prostate cancer risk in forty patients newly diagnosed with prostate cancer and fifty-eight hospital controls recruited in two provinces from southern and northern Italy. We found an excess cancer risk in subjects in the third and fourth (highest) quartiles of toenail cadmium concentration (odds ratio 1.3 and 4.7, respectively) compared with subjects in the bottom quartile. Results were basically unchanged when limiting the analysis to each province or entering toenail cadmium concentrations as continuous values in the regression model (P=0.004). Despite the limited statistical stability of the point estimates, these findings appear to support the hypothesis that cadmium exposure increases prostate cancer risk.