This study was undertaken to confirm the utility of systematic transrectal ultrasound-guided prostate biopsy in diagnosing cancer in patients with abnormal findings on digital rectal examination or abnormal levels of prostate-specific antigen (or both). The authors also wanted to determine the diagnostic advantage of taking six sextant biopsy samples rather than four quadrant samples. In a prospective study of 669 men examined between July 1992 and April 1993 at a tertiary-care hospital, core samples were obtained from any visualized or palpated abnormalities, the three other "normal" quadrants (apices and bases) and the two parasagittal midzones. The glands of 403 of the patients (60%) had an abnormality detectable by ultrasonography, and 233 of the patients (35%) had adenocarcinoma, proven by histologic examination. Of the 169 cases of adenocarcinoma initially indicated by ultrasonography, the suspected lesion was histologically benign in 66 (39%), but malignancy was found in another portion of the gland. In 18 (8%) of the 233 patients with adenocarcinoma, the only positive result was obtained from the additional core biopsy samples from the midzone. This study confirms that the ultrasonographic characteristics of cancer are variable, that many tumours (130 [56%] in this study) are detected in areas that are normal on ultrasonography and digital rectal examination, and that the detection sensitivity is increased (by 8% in this study) when two midlobe parasagittal plane biopsy samples are added to the four standard quadrant samples.