18F-fluorodeoxyglucose-positron emission tomography/ computed tomography (18F-FDG PET/CT) is a widely used diagnostic tool for whole-body imaging, and incidental prostatic uptake occurs in approximately 1% of patients undergoing the exam. Is 18F-FDG PET/CT a reliable screening tool for prostate cancer? Should these patients undergo transrectal ultrasound (TRUS)-guided prostate biopsies? Studies have indicated that 18F-FDG PET/CT has a low positive predictive value for prostate cancer and is not recommended for screening;1 however, other studies suggest that when a discrete focal 18F-FDG uptake is discovered without coincidental calcification, particularly in the peripheral zone of the prostate, further clinical evaluation is recommended. We present two patients with incidental 18F-FDG PET/CT prostatic uptake who were found to have high-grade prostate cancer. Although 18F-FDG PET/CT has not been determined to be a reliable screening tool for prostate cancer, patients with incidental 18F-FDG uptake in the prostate should be referred for urological evaluation.