OBJECTIVE: To investigate if prostate biopsy templates with fewer cores can be used during active surveillance (AS) for prostate cancer. METHODS: At present, we use an AS protocol template (ASPT) consisting of 13-17 cores. We hypothesize in the setting of known cancer, sextant (6 cores) or standard extended (10-12 cores) templates, could be used with similar effect. We identified patients in our referral institution database (1997-2009) with entry prostate-specific antigen <10 ng/mL, stage ≤cT2, Gleason sum ≤6, ≤3 cores positive for cancer, <50% of single core involved, and age ≤75 years (N = 272). Patients fulfilling standard criteria for pathologic reclassification (N = 94) at any follow-up biopsy were selected for evaluation. By mapping tumor location on the pathologic reclassification determining biopsy, hypothetical scenarios of sextant or standard extended templates (SET) were compared with our ASPT and examined for frequency of cancer detection and pathologic reclassification. RESULTS: For the 94 patients analyzed, the median number of cores taken was 9.7 (6-22) at baseline and 15 (14-17) for the reclassification biopsy. The median time between baseline and the pathologic reclassification determining biopsy was 15.4 months. Analysis of subgroupings showed that sextant template would identify 84% of cancers and 47.9% of the reclassification events, whereas SET detected 99% of cancers and 81.9% of patients who pathologically reclassified. When only considering Gleason sum ≥7 related progression events, SET found 16.2% less (n = 57) compared with ASPT (n = 68). CONCLUSION: When monitoring patients on AS, a 13-17 core template detects more pathologic reclassification than standard sextant (18.1%) or extended (52.1%) biopsy templates.