Objective: To analyze the impact of 2 systematic transition zone (TZ) biopsies in addition to systematic sextant biopsies in an effort to establish the importance of cancer detected in the transition zone. Methods: Between November 1995 and October 1996, TRUS-guided systematic sextant peripheral zone (PZ) and two additional TZ biopsies were performed on 189 consecutive men. Radical retropubic prostatectomy (RRP) was performed to 13 patients with organ-confined prostate cancer. The biopsy results of the 52 patients with cancer and the pathological specimens of the patients who underwent surgery were compared. Results: Of the 189 patients, 52 (27.5%) had prostate cancer of whom 20 (38.5%) both in the PZ and TZ, 31 (59.6%) only in the PZ, and 1 (1.9%) in the TZ only. Of the 96 patients with high serum PSA levels despite normal DRE, 14 had prostate cancer. TZ cancer only rate was 7.1% (1 in 14 patients) in this group. RRP was performed to 8 patients who had cancer only in the PZ and 5 patients in both TZ and PZ. The pathological stages of the postoperative specimens and extracapsular extension rates of those with cancer in the PZ and TZ were significantly higher (p = 0.029 and p = 0.008, respectively). Conclusions: Routine TZ biopsy does not substantially increase the prostate cancer detection rate, however it can be useful in selected patient groups. If further studies reveal the relationship of cancer in the transition zone, higher capsular extension rate (pT3 cancer) and higher pathological stage after radical surgery, then TZ biopsies may yield additional information that might influence the therapeutic approach.