INTRODUCTION: To evaluate Prostate Cancer Prevention Trial (PCPT) risk calculator versus prostate cancer gene 3 (PCA3) score versus case-finding protocol accuracy in prostate cancer diagnosis in patients with prostate-specific antigen (PSA) below 10 ng/mL submitted to repeat saturation biopsy (SPBx). MATERIALS AND METHODS: From December 2010 to December 2011, 100 patients (median 66 years) underwent a SPBx (median 30 cores); the indications for repeat biopsy were those of a case-finding protocol: PSA values between 4.1 ng/mL-10 ng/mL or 2.6 ng/mL-4 ng/mL with F/T PSA ≤ 25% and ≤ 20%, respectively. All patients had negative digital rectal examination (DRE) and median PSA was 7.9 ng/mL. The performance of PCPT risk calculator (alone, combined with PSA free/total ( F/T) or PCA3 score) and PCA3 score in comparison with the case-finding protocol results (alone or combined with PCA3 score) was retrospectively evaluated in terms of detection rate for cancer and number of avoided biopsies. RESULTS: Prostate cancer was found in 28 (28%) patients; in the presence and absence of prostate cancer median PCA3 score was 57 versus 35 (p < 0.05). Using PCPT risk calculator (cut off probability of 25%) combined with PCA3 score no prostate cancer would be missed avoiding 8% of unnecessary biopsies. PCA3 score > 20 missed 7.2% of cancer; the case-finding protocol combined with PCA3 score > 35 would save 22% of avoidable biopsies, missing no cancer if all patients with PSA F/T â¤ 15% would undergo prostate biopsy irrespective of PCA3 values. CONCLUSIONS: PCA3 score improves PCPT risk calculator accuracy in prostate cancer diagnosis; moreover, PCA3 score combined with PSA F/T reduce number of unnecessary biopsies (about 20%).