15533 Background: Prostate cancer remains undetected in approximately one-third of patients following standard transrectal ultrasound-guided biopsy. In this study, we evaluated prostate cancer incidence, anatomic distribution, Gleason score profile and tumor burden in patients diagnosed by transperineal template-guided saturation biopsy (TTSB). Methods: One hundred and seventeen patients underwent TTSB. TTSB was performed under general anesthesia. All but one patient had undergone at least one prior negative TRUS biopsy. Criteria for inclusion included an elevated PSA and/or the diagnosis of ASAP or high-grade PIN on prior biopsy. The prostate gland was divided into 24 regional biopsy locations with 1–3 biopsies per region. The median number of biopsy cores was 50. Multiple clinical parameters were evaluated as predictors for prostate cancer diagnosis. Results: The mean patient age was 64.8 years with a mean PSA of 9.1 ng/mL and a prostate volume of 78.6 cm3. On average, patients had undergone 2.1 prior negative TRUS biopsies with a mean of 22.4 core biopsies. Prostate cancer was diagnosed in 49 patients (41.9%) with a Gleason score distribution of 6–9. Patients with a prostate volume of = 60 cm3 had a higher rate of cancer diagnosis compared to patients with larger glands (66% vs. 30%). Although no anatomic region of the prostate gland was spared of cancer, there was a preponderance of anterior-based malignancies. In patients with prostate cancer, an average of 9.9 cores were involved. In multivariate analysis, pre-saturation biopsy diagnosis and prostate volume were the best predictors for prostate cancer diagnosis. Conclusions: Transperineal template-guided saturation biopsy diagnosed prostate cancer in 41.9% of previously biopsied patients. Considerable anatomic variability in prostate cancer distribution was documented. Based on this and other reports, cancer eradication will be dependent on treatment of the entire prostate gland. No significant financial relationships to disclose.