A study was conducted to compare results of transrectal ultrasound with pathologic findings on 116 patients who underwent radical prostatectomy for treatment of prostate cancer. In 96% (111 of 116), transrectal ultrasound guided biopsies of a hypoechoic lesion proved cancer; seven patients had known Stage A cancer; one patient had cancer detected by palpation and not detected by ultrasound. Cancers in the outer gland (peripheral and central zones) were compared with cancers in the inner gland (transition zone) by both ultrasound and pathology. Forty-eight percent (52 of 108) of cancers originating in the outer gland showed extraprostatic extension (Stage C disease). The primary sites of tumor escape from the outer gland were the prostatic capsule (38%), anterior fibromuscular stroma (5%), seminal vesicle (18%), the base of the gland at the neurovascular bundle (21%), and the apex (31%). Twenty-two percent (17 of 54) of cancers originating in the inner gland (transition zone) showed extraprostatic extension (Stage C disease). The primary sites of tumor escape from the inner gland were the anterior fibromuscular stroma (6%) and apex (11%). Both histologic and biologic differences between outer and inner gland cancers were found when tumor size was controlled. Gleason scores were significantly different for inner and outer gland cancers, with mean scores of 6.2 +/- 1.6 and 7.4 +/- 0.9, respectively. An odds ratio of 8.6 confirmed the increased risk of extraprostatic extension for outer gland cancer. Outer gland cancers showed increased aggressive behavior of both histologic and biologic nature. The difference in biologic aggressiveness of outer and inner gland cancers has definite implications for treatment options. Use of other diagnostic parameters, such as DNA ploidy, may help to determine which cancers to treat and when to treat them; this may have more relevance for cancers originating in the inner gland. Strategic transrectal ultrasound guided biopsy affords accurate tumor mapping and staging when modes of internal spread and escape of cancer from both outer and inner gland are known. Thus, transrectal ultrasound may be our "window of observation" through which additional research may explain the histologic and biologic discrepancies between outer and inner gland cancers.