With prostate and colorectal malignancies being the most common cancers in men, elevated prostate specific antigen (PSA) in patients without rectal access due to prior surgery poses a diagnostic dilemma. We report the first use of CT-guided biopsy in combination with prebiopsy MRI in 2 patients with a clinical suspicion of prostate cancer and no rectal access. In both cases, a diagnostic multiparametric MRI of the prostate was performed to detect and to localize a potential suspicious lesion. The localization served as a cognitive map for guiding needle placement using a CT-guided transgluteal approach.