Abstract Purpose Men diagnosed with atypical small acinar proliferation (ASAP) are counseled to undergo early re-biopsy, as their risk of prostate cancer (PCa) is high. However, random re-biopsies may not re-sample areas of concern. Magnetic resonance imaging/transrectal ultrasound (MRI/TRUS) fusion-guided biopsy offers an opportunity to accurately target, and later re-target, specific areas within the prostate. The purpose of this study is to describe the ability of MRI/TRUS fusion-guided prostate biopsy to detect PCa in areas with an initial diagnosis of ASAP. Materials and Methods From March 2007 to February 2014, 1,028 patients underwent MP-MRI of the prostate and MRI/TRUS fusion-guided biopsy. Twenty patients met the following stringent inclusion criteria: no history of PCa; index biopsy demonstrating at least one core of ASAP and benign glands in all remaining cores; fusion targeted re-biopsy with at least one targeted core directly re-sampling an area of the prostate which previously contained ASAP. Results At index biopsy, the 20 patients had a median age of 60 years (IQR 57-64) and median PSA of 5.92ng/ml (IQR 3.34-7.48). At fusion targeted re-biopsy in a median 11.6 months, 5/20 (25%, 95% CI 6.02-43.98) patients were diagnosed with PCa, all of which was primary Gleason grade 3, low-volume disease. On fusion re-biopsy, cores which directly re-targeted areas of previous ASAP detected the highest tumor burden. Conclusions When MRI/TRUS fusion-guided biopsy detects isolated ASAP on index biopsy, early re-biopsy is unlikely to detect clinically significant PCa. Cores which re-target areas of previous ASAP are more effective than random re-biopsy cores.