Aim: To evaluate the diagnostic value of 10+ systematic sampling technique when performing transrectal ultrasound-guided (TRUS) prostate biopsy, compared with the sextant biopsy technique for patients with suspected prostate cancer. Methods: 286 patients with suspected prostate cancer were included in the study. Patients were eligible for the study if they had serum levels of prostate-specific antigen (PSA) >4 ng/ml or ratio PSA <0.25 and/or an abnormal digital rectal examination (DRE). The population sample was divided in three groups: (1) those with positive PSA, PSA ratio and DRE (70 patients); (2) those with positive PSA and PSA ratio but normal DRE (178 patients), and (3) those with positive PSA and PSA ratio, positive PSA velocity and a negative biopsy in the previous 6-month period (38 patients). In addition to the conventional sextant prostate biopsy cores, four more biopsies were obtained from the lateral peripheral zone (10 core biopsy protocol). Additional cores (total of 12–14) were also randomly selected in case of larger prostates (>60 ml) or from suspicious foci revealed by transrectal ultrasound. All additional biopsy cores were submitted separately to the pathological department. Results: Cancer was detected in 55.7% (39/70) and 69% (48/70) of the patients (for sextant core and for the extended biopsy protocols, respectively) in the first study group, 11% (20/178) and 23% (41/178) of the patients (for the sextant and the extended biopsy protocols, respectively) in the second study group, and 42% (16/38) and 63% (24/38) of the patients (for the sextant and the extended biopsy protocols, respectively) in the third study group. The addition of the lateral peripheral zone (PZ) of the prostate to the sextant biopsy showed a 23, 105 and 50% increase in the number of cancers diagnosed in the first, second and third study groups, respectively. The improvement of cancer detection rate (sensitivity) was statistically significant for all groups evaluated. Conclusion: The 10+ systematic TRUS-guided prostate biopsy improves the detection rate of prostate cancer compared to the sextant biopsy technique alone, especially when performed in men with positive PSA, PSA ratio, and negative DRE.