To validate the role of mpMRI combined to CAD system, to increase prostate cancer detection rate using TRUS-MRI guided biopsy. 167 individuals, with elevated PSA level and no previous positive biopsy were enrolled and 63 underwent targeted biopsy. Two radiologists evaluated the exams adopting PIRADSv2 and CAD system. Radiologists’ evaluation proved better diagnostic performance compared to CAD. The highest detection rate for clinically significant cancer was obtained biopsying “target into target” lesions. CAD system proved to be useful in pinpointing the neoplastic area within MRI lesions, representing a valuable tool in identifying biopsy targets to improve CDR.