Objectives. To determine the accuracy of different combinations of biopsies in detecting prostate cancer. The standard sextant protocol for obtaining prostate biopsy underestimates the presence of prostate cancer. Conversely, an increased cancer detection rate has been obtained with additional laterally directed biopsies. The results of the studies dedicated to transrectal color Doppler (CD) sonography have shown that it might detect neoplastic lesions with no corresponding gray-scale abnormality. Methods. A total of 120 consecutive patients underwent sextant biopsy with additional biopsy cores taken from the lateral peripheral zone (four to six cores, depending on the prostate volume) and CD-guided biopsy. The sensitivity of laterally directed, CD-guided, and different combinations of biopsies was compared. Various patient, clinical, and pathologic factors were compared, and multivariate analysis was performed to assess the strongest predictor of cancer detection. Results. Cancer was detected in 43 (35.8%) of 120 patients. The combination of sextant biopsy with laterally directed cores gained sensitivity to 56.6% compared with 67.4% obtained in the regimen that combined sextant and CD-guided biopsy. The CD regimen detected cancer in 11 additional patients. However, the differences in the detection rates of these combinations were not statistically significant (P = 0.797). The results of multivariate analysis showed that sextant biopsy and laterally directed cores were the strongest predictors of cancer detection (odds ratio 8.356 versus 49.282; 95% confidence interval 1.698 to 41.114 versus 10.508 to 231.130). Conclusions. The regimen that included sextant and CD-guided biopsy was the most sensitive. However, only standard sextant and laterally directed biopsies were statistically significant predictors of cancer detection on biopsy.