OBJECTIVE: To evaluate the accuracy in histologic grading of MRI/US image fusion biopsy by comparing histopathology between systematic biopsies (SB), targeted biopsies (TB) and the combination of both (SB + TB) with the final histopathologic outcomes of radical prostatectomy specimens. MATERIALS AND METHODS: Retrospective, multicentric study of 443 patients who underwent SB and TB using MRI/US fusion technique (Urostation and Trinity) prior to radical prostatectomy between 2010 and 2017. Cochran's Q test and McNemar test were conducted as a post hoc test. Uni-multivariable analyses were performed on several clinic-pathological variables to analyze factors predicting histopathological concordance for targeted biopsies. RESULTS: Concordance in ISUP (International Society of Urological Pathology) grade between SB, TB and SB + TB with final histopathology was 49.4%, 51.2%, and 63.2% for overall prostate cancer and 41.2%, 48.3%, and 56.7% for significant prostate cancer (ISUP grade ≥ 2), respectively. Significant difference in terms of concordance, downgrading and upgrading was found between SB and TB (ISUP grade ≥ 2 only), SB and SB + TB, TB and SB + TB (overall ISUP grade and ISUP grade ≥ 2) (p < 0.001). Total number of cores and previous biopsies were significant independent predictive factors for concordance with TB technique. CONCLUSION: In this retrospective study, combination of SB and TB significantly increased concordance with final histopathology despite a limited additional number of cores needed.