The number of patients undergoing prostate biopsy has dramatically increased due to prostate specific antigen screening. The low specificity of this screening tool requires prostate biopsy for diagnosis of prostate cancer. The sextant biopsy technique has been used widely with success in diagnosing carcinoma of the prostate. However, concern has arisen that the original sextant method may not include an adequate sampling of the prostate. For many years we have used a method of prostate biopsy that, in addition to sextant biopsies, takes additional biopsies in a systematic fashion, which we call the 5 region prostate biopsy. We conducted a prospective study to determine if our 5 region prostate biopsy technique significantly increases the chances of finding carcinoma of the prostate compared to the sextant biopsy technique. A total of 119 patients underwent transrectal ultrasound guided needle biopsy of the prostate. In addition to sextant biopsies, cores were taken from the far lateral and mid regions of the gland. Pathological findings of the additional regions were compared to those of the sextant regions. Of the 48 patients with prostate cancer 17 (35%) had carcinomas only in the additional regions, which would have remained undetected had the sextant biopsy technique been used alone (p < 0.05). Of these additional cancers 83% had Gleason scores of 6 or more. We introduce the 5 region technique of prostate biopsy as a means of significantly increasing the diagnostic yield of prostate biopsy in finding carcinoma of the prostate. We have found this technique to be safe, efficacious and superior to the sextant method of biopsy in identifying prostate cancer at an early but significant stage. The greatest use of the 5 region biopsy technique is in patients who have prostate specific antigen levels between 4 and 10 ng./ml.