Focal therapy of prostate cancer (PCa) is currently of great interest, but a metric of success. other than biopsy, is not yet available. In a patient with a repeatedly negative MRI and negative systematic biopsies, a scan employing the radioisotope 68Ga-PSMA-11 PET/CT identified a PSMA-avid hotspot in the prostate. PSMA-guided biopsy confirmed the diagnosis of a clinically-significant PCa. Following ablation of the lesion with high-intensity focused ultrasound (HIFU), the PSMA-avid lesion disappeared and targeted biopsy confirmed a fibrotic scar with no residual cancer. PSMA imaging may have a role in guiding diagnosis, focal ablation, and follow-up of men with PCa.