After comprehensively screening HSD17B1 for variation in U.S. and European whites, we found no evidence of association between prostate cancer and common variants in HSD17B1. We observed that haplotype odds ratios for association with prostate cancer differed across ethnicity, with the CAGC haplotype showing a significant (p < 0.01) inverse association with prostate cancer effects in Latinos and Japanese Americans. Here, HSD17B1 is linked to prostate cancer.