Systematic biopsies are a useful, sensitive means to detect carcinoma of the prostate. However, multiple biopsies pose a risk for detecting clinically insignificant prostate cancer, that is those cancers less than 0.5 cc in volume, which occur in approximately 32% of all white men more than 50 years old. Systematic biopsies were positive for cancer in 442 of 816 patients and 60 (14%) demonstrated only a minute focus of cancer (3 mm. or less) in 1 of the 6 biopsy specimens. In 27 patients with these minute foci who underwent radical prostatectomy a wide range of cancer volumes was observed; 30% of these 27 cancers were less than 0.5 cc (15% less than 0.2 cc) and may not have required therapy. Thus, the overall risk of detecting an insignificant cancer is 4.0% with systematic biopsies. Performance of confirmatory biopsies in patients with a minute focus (3 mm. or less) of cancer on initial systematic biopsies resulted in cancers less than 0.5 cc being removed in only 1 of 10 radical prostatectomies (10%, none was less than 0.2 cc). Thus, with the addition of confirmatory biopsies the risk of detecting insignificant cancer is 1.4%. Conservative management is recommended for patients without significant cancer on repeat biopsies in whom initial biopsies have revealed only a minute focus of cancer in 1 of the biopsy cores. We believe that concern is also warranted for patients who have 3 mm. or less of cancer demonstrated by several nonsystematic biopsies directed at a suspicious hypoechoic lesion in whom the digital rectal examination is normal.