A nested case-control study was conducted to determine whether a genetic polymorphism in the CYP17 gene, which encodes for an enzyme that mediates steroid hormone metabolism, was associated with an increased risk of breast cancer. No association was found between the presence of an A2 allele and the subsequent development of breast cancer [A1/A2 odds ratio, 0.61 (95% confidence interval, 0.33-1.14); A2/A2 odds ratio, 0.89 (95% confidence interval, 0.41-1.95)]. No significant association was observed with risk factors presumed to be surrogates for endogenous estrogen exposure, nor was there an association observed with the stage of disease at diagnosis. Genotype frequencies in this Caucasian population were similar to those reported for African-American, Asian, and Latino women. Additional studies of larger size are needed to achieve a consensus regarding the relevance of CYP17 genotypes to the risk of developing breast cancer.