Introduction The widespread screening for PSA has contributed to the increased incidence of prostate cancer (PCa), mostly identifying disease at earlier stages. Many of these patients will probably not require treatment because of the indolent course of the disease. The European Randomized Study of Screening for Prostate Cancer (ERSPC) has showed that 1410 men needed to be screened and 48 prostatectomies performed to prevent death. The aim of this study was to evaluate predictive factors of insignificant PCa in our experience. Materials and Methods We analyzed various preoperative clinical and biopsy findings of 225 consecutive patients who underwent prostatectomy from October 2007 to June 2010. The indication for biopsy was placed in presence of an abnormal rectal examination and/or suspected transrectal ultrasound and/or PSA >4 ng/ml. We consider insignificant a tumor with a volume ≤5% of the entire gland with a Gleason score ≤ 6, with no grades 4 or 5 and organ confined. Results The prevalence of potentially insignificant PCa in our experience was 12%. The preoperative findings of patients with insignificant PCa were significantly more favorable than the remaining cases with PCa not insignificant. Multivariate analysis did not reveal any independent predictors. Conclusions In our experience, in a population not screened for PCa, we have not identified any factors that can predict with certainty the insignificant nature of a tumor and, therefore, useful to start a patient on an active surveillance program.