The decision to proceed with radical prostatectomy has to be supported with biopsy-proven prostate cancer. However, when a patient has persistently multiple negative prostate biopsies and a high PSA, a serious diagnostic and therapeutic dilemma arises. The PIRADS score generated by the multiparametric-MRI of the prostate provides a guide for a template biopsy using MRI-ultrasound fusion technology, with the hope of minimizing a false negative result. Fluorine-18 Prostate-Specific Membrane Antigen (18F-PSMA) PET CT scan, on the other hand, is used mainly for staging prostate cancer after biochemical recurrence. The use of 18F-PSMA PET CT in the primary clinical diagnosis of prostate cancer has never been reported.The authors performed radical prostatectomy on a 66-year-old HIV-positive male with suspicious lesion on 18F-PSMA, PIRADS 5 on mp-MRI, and a persistently elevated PSA >100 despite multiple negative biopsies. The final histopathological analysis confirmed the presence of adenocarcinoma of the prostate, Gleason 7 (3+4), with negative margins. There were no intraoperative complications, and the patient was discharged in good condition. On follow-up, he had a nadir PSA of 0.058 ng/ml, has partial incontinence, and decreased erectile function and was advised phosphodiesterase inhibitors. 18F-PSMA may be utilized in the decision process for patients who are highly suspected with malignancy but have no preoperatively biopsy-proven cancer after multiple negative biopsies.