Background: Prostate cancer is the most common malignancy among the male population in the United States and the 3rd most common non-skin cancer among men in Iran. Its prevalence has shown a rising trend in recent decades. The aim of this study was to report the epidemiological features of prostate cancer in patients referred for prostate biopsy in the south of Iran and to evaluate the accuracy of the levels of the prostate-specific antigen (PSA) and the PSA-density (PSAD) as well as the extension of the disease in the prediction of the biological behavior of prostate cancer.Methods: This is a retrospective study on the medical records of 1982 consecutive patients who underwent transrectal ultrasound-guided biopsy due to an abnormal digital rectal examination and/or an elevated PSA level following referral from the Urology Ward to the Radiology Department of Shahid Faghihi Hospital in Shiraz, southern Iran, between December 2003 and July 2014.Results: The overall cancer detection rate was 33.1%. Although the cancer was more prevalent among the elderly patients, a significant fraction (7%) of the patients were aged < 55 years. The sensitivity and specificity of the PSA were 97.4% and 8.7% and those of the PSAD were 82.9% and 52%, respectively. Of the 637 patients with prostate cancer, 250 (39.2%) had unilateral disease, 378 (59.4%) had bilateral disease, and 9 (1.4%) had inner-gland involvement. Most of the patients with bilateral involvement had high-grade Gleason scores.Conclusion: Our study underlines the relationship between age and the frequency of cancer; the levels of the PSA and the PSAD and the Gleason score; and the extent of tumor involvement and the grade of prostate cancer and also highlights the significance of screening, especially in younger patients.