OBJECTIVES: To assess cancer detection rates of different target-dependent transperineal magnetic resonance (MR)/ultrasonography (US) fusion-guided biopsy templates with reduced number of systematic cores. PATIENTS AND METHODS: Single-centre outcome of transperineal MR/US fusion-guided biopsies of 487 men with a single target MR imaging (MRI) lesion, prospectively collected between 2012 and 2016. All men underwent transperineal targeted biopsy (TB) with two cores, followed by 18-24 systematic sector biopsies (SB) using the Ginsburg protocol. Gleason score ≥7 prostate cancer detection rates for two-core TB, four-core extended TB (eTB), 10- to 20-core saturation TB (sTB) including cores from sectors adjacent to the target, and 14 core ipsilateral TB (iTB) were compared to combined TB+SB. RESULTS: Cancer was detected in 345 men and Gleason score 7-10 cancer in 211 men. TB alone detected 67%, eTB 76%, sTB 91% and iTB 91% of these Gleason score 7-10 cancers. In the subgroup of 33 men (7% of cohort) with an anterior >0.5 mL highly suspicious MRI lesion and a prostate volume ≤45 mL, four-core eTB detected 31 of 32 cancers (97%) and all 26 Gleason score 7-10 cancers. CONCLUSION: sTB detected Gleason score 7-10 cancer in 25% more of the men than a two-core TB approach, and in almost as many men (91%) as the 20-26-core combined TB+SB, while needing only 10-20 cores. A four-core extended TB may suffice for large, highly suspicious anterior lesions in small or slightly enlarged prostates.