Prostate Specific Antigen has been widely used in diagnosis and management of patients with prostate cancer. It may be elevated in other prostatic diseases. The objective of this study was to evaluate its efficacy to diagnose and differentiate between benign and malignant enlargements. Study also determines relationship between serum prostate specific antigen levels and histopathologic findings in prostatic biopsies. Materials and Methods: Study was done at a tertiary care hospital in Telangana over 6 years. A total of 500 patients were included in the present study. Prior to surgery serum prostate specific antigen levels were determined for all the cases and the biopsies were sent for histopathology. Results: In the present study mean age of presentation was 64.24 years. Amongst the 500 cases, 451 (90.2%) were of Benign Prostatic Hyperplasia, 32 (6.4%) were of Prostatic Intraepithelial Neoplasia and 17 (3.4%) were of Prostatic Adenocarcinoma. Serum prostate specific antigen levels range distribution was considered into 3 groups as: 04 ng/ml included 404 (80.8%) cases, 59 ng/ml with 44 (8.8%) cases and 10 ng/ml included 52 (10.4%) cases. Present study revealed sensitivity 70%, specificity 91%, diagnostic accuracy 91%, positive predictive value 23%, and the negative predictive value 98%. Conclusion: PSA is specific for prostate but not for prostate cancer. PSA is raised in cancer, prostatic infection, urinary retention & Nodular Prostatic Hyperplasia. There is need of a more reliable and precise serum marker that reflects prostate cancer.