Tissue inflammation has been linked to cancer in several disease models. We tested the association between chronic inflammation and prostate cancer (PCa), as well as high-grade prostatic intraepithelial neoplasia (HGPIN), in prostatic needle biopsy specimens. Tissues from 4526 men, who underwent systematic ultrasound-guided sextant needle biopsies of the prostate, were classified in the following order as PCa, or HGPIN, or chronic inflammation or benign. PCa was diagnosed in 1633 (36.1%), HGPIN in 535 (11.8%) and chronic inflammation in 347 (7.7%). Chronic inflammation conferred a protective effect from PCa: odds ratio (OR) = 0.20, 95% confidence interval (CI) = 0.15-0.28. Chronic inflammation was also inversely associated with HGPIN: OR = 0.11, 95% CI = 0.05-0.22. The ORs remained virtually unchanged after adjustment for age, serum prostate-specific antigen (PSA), digital rectal examination (DRE) and gland volume. Chronic inflammation is more frequent in the presence of benign histology than it is in the presence of PCa or HGPIN.