PURPOSE Certain Y-chromosomal lineages have been suggested to predispose individuals to prostate cancer in the Japanese population; in other ethnic groups, however, the importance of the Y chromosome is poorly understood. EXPERIMENTAL DESIGN To assess the possible Y-chromosomal contribution to prostate cancer risk and prognosis, we analyzed five binary Y-chromosomal markers in 1,447 prostate cancer cases and 983 population controls from the Swedish population. Together, these five markers capture the vast majority of chromosome Y haplogroup diversity in the Swedish population. Individual lineages were tested for association with both prostate cancer risk and cancer-specific death. We replicated observed associations in an independent Swedish prostate cancer case-control study comprising 1,452 cases and 779 controls. RESULTS One rare lineage (I1c) was associated with an increased risk of developing prostate cancer [odds ratio (OR), 2.9; 95% confidence interval (CI), 1.4-5.8; P = 0.001]. However, confirmatory analysis of this lineage in the independent case-control study revealed no association with prostate cancer risk (OR, 0.65; 95% CI, 0.4-1.2, P = 0.17). We observed no association between chromosome Y variation and prostate cancer-specific death. CONCLUSIONS This study provides strong evidence against an important role of the Y chromosome in the initiation or outcome of prostate cancer in the Swedish population.