A total of 71 patients with clinically localized prostatic cancer underwent preoperative biopsy of each seminal vesicle. Group 1 (67 patients) underwent 2 seminal vesicle biopsies before lymph node dissection and vesiculo-prostatectomy, while group 2 (4 patients) underwent seminal vesicle biopsy and lymph node dissection before radiation therapy. In group 1 there were 11 positive biopsies (16.5%) with a median prostate specific antigen (PSA) level of 24 ng./ml. (range 11 to 45). Of the biopsies 56 were normal, with a median PSA level of 11.8 (range 3.5 to 88, p < 0.008). Histological examination of the seminal vesicles on the prostatectomy specimen revealed 18 cases of seminal vesicle invasion (sensitivity 61%, specificity 100%, positive predictive value 100% and negative predictive value 87.5%). A positive biopsy was correlated with the mean tumor volume (10.3 cc with positive biopsies versus 4.9 cc with negative biopsies) and local invasion (positive margins in 36% versus 9%, respectively, and capsular perforation in 81% versus 25%, respectively). In group 2 the 4 seminal vesicle biopsies and lymph node dissections were positive. Overall (groups 1 and 2), positive seminal vesicle biopsies were predictive of lymph node involvement in 47% of the cases versus 7% when biopsies were negative (p > 0.001). The postoperative course was significantly different (local recurrence and metastases in 45% versus 9%, respectively, and median interval 8.8 months versus 18.3 months, respectively, p < 0.001). Seminal vesicle biopsy appears to have a satisfactory yield only in cases with a PSA level of greater than 10 ng./ml. A positive seminal vesicle biopsy confirms the presence of extraprostatic invasion of clinically localized cancer in a given patient. Seminal vesicle biopsy allows for better staging of prostatic cancer.