INTRODUCTION: Limited data exist on long term pathological outcomes in patients with initial prostate biopsies showing either high-grade intraepithelial neoplasia (HGPIN) or benign findings, who are subsequently diagnosed with prostate cancer. MATERIALS AND METHODS: Preoperative characteristics of patients showing either HGPIN or benign initial prostate biopsies were investigated and compared in patients with and without a subsequent diagnosis of prostate cancer. We also compared the biopsy and prostatectomy findings in patients with prostate cancer in both groups. RESULTS: We evaluated 161 and 85 patients with initial HGPIN and benign prostate biopsies, respectively, who underwent a subsequent biopsy. After a median follow up of 11 years, prostate cancer was detected in 26.7% patients after HGPIN and in 22.3% patients after initial benign biopsy. Ninety-eight percent of positive biopsies after initial HGPIN demonstrated either Gleason score (GS) 3 + 3 (86%) or GS 3 + 4 (12%). In the benign group, 100% of patients demonstrated prostate cancer on biopsy with either GS 3 + 3 (58%) or GS 3 + 4 (42%). Of 35 patients who underwent prostatectomy (22 after initial HGPIN biopsy and 13 after initial benign biopsy), all had node negative, organ-confined disease; 86% and 54% patients had GS6 disease, with = 5% tumor volume found in 91% and 62% of the HGPIN and benign group, respectively. CONCLUSIONS: Patients with initial HGPIN or benign biopsies preceding a diagnosis of prostate cancer usually show favourable pathology on positive biopsy and prostatectomy, most commonly exhibiting low volume and low grade disease. These findings may help clinicians risk-stratify patients who may benefit from conservative management options.