The enzyme product of SRD5A2, 5alpha-reductase type II, is responsible for converting testosterone to the more metabolically active dihydrotestosterone. Therefore, SRDSA2 may be involved in the development or growth of prostate tumors. To examine the effects of allelic variants in the gene SRDSA2 on the presentation of prostate tumors, we studied a sample, primarily Caucasian, of 265 men with incident prostate cancer who were treated by radical prostatectomy. We assessed the relationship of the A49T and V89L polymorphisms at SRD5A2 with clinical and pathological tumor characteristics of these patients. We found no association of V89L genotypes with any of the characteristics studied. The presence of the A49T variant was associated with a greater frequency of extracapsular disease [odds ratio (OR), 3.16; 95% confidence interval (CI), 1.03-9.68] and a higher pathological tumor-lymph node-metastasis (pTNM) stage (OR, 3.11; 95% CI, 1.01-9.65). In addition, the A49T variant was overrepresented in two poor prognostic groups, which have been correlated with reduced rates of biochemical disease-free survival. One group included men with at least two of the following poor prognostic variables: (a) stage T3 tumor; (b) PSA level >10; and/or (c) Gleason score, 7-10 (OR, 3.46; 95% CI, 1.04-11.49). The second group included men with positive margins and high Gleason score (OR, 6.28; 95% CI, 1.05-37.73). Our results suggest that the A49T mutation may influence the pathological characteristics of prostate cancers and, thus, may affect the prognosis of these patients.