Objective: Prostate cancer has its most frequent location in the posterior-lateral part of the gland. The aim of this study was to evaluate the cancer detection rate of six systemic prostate biopsies with mid lobar biopsies taken far laterally in the prostate. Patients and Methods: A total of 692 patients (aged 50-66 years) enrolled in a screening study underwent prostate biopsies because of an elevated serum prostate-specific antigen (PSA; greater than or equal to3 ng/ml) level. The outcome of the biopsies was related to findings at digital rectal examination (DRE) and transrectal ultrasound (TRUS) and to the location within the prostate. Results: Prostate cancer was detected in 164 patients. DRE and TRUS were suspicious of malignancy in 66 cases (40%) and 84 cases (51%), respectively. The two biopsies taken far laterally midlobar in the prostate detected as many as 83% of the cancers and when combined with two apical biopsies, 96% of all cancers were detected. Conclusion: At PSA screening in this age-group, only 57% of the prostate cancers detectable by sextant biopsies were palpable or visible at TRUS. Most of the cancers (96%) were detectable by only four systematic, carefully directed biopsies. In men with normal DRE, the two lateral midlobar biopsies should be taken first during the biopsy procedure. Copyright (C) 2001 S. Karger AG, Basel.