The increase in the global incidence of prostate cancer (PCa) and benign prostate hyperplasia (BPH) can be adduced to increase in life expectancy, as both disorders are associated with aging. Prostate specific antigen (PSA) a pioneer biochemical marker for screening and diagnosis of prostate disorders has been found to be of limited specificity in differentiating PCa and BPH from prostatitis. We thus evaluated the role of fibroblast growth factor 23 (FGF-23) and estradiol (E2) in the development and progression of prostate disorders, their specificity and sensitivity in prostate disorders and the possible use of serum FGF-23 level as a diagnostic index for PCa and BPH. Thirty patients each with histological diagnosis of PCa or BPH were recruited from the Urology Unit of the University College Hospital Ibadan, and thirty aged-matched controls. Serum FGF-23, E2 and tPSA were assayed by ELISA technique and data generated, analyzed with IBM SPSS version 20.0 and Receiver Operating Characteristics (ROC) curve. The mean tPSA was found to be significantly higher (17.78 vs 5.25) and (17.78 vs 2.33) in PCa participants compared with BPH participants and controls respectively. FGF-23 was significantly higher in patients with PCa and BPH when compared with controls; (224.12 vs 207.33) and (222.88 vs 207.33) respectively. FGF-23 significantly differentiated participants with prostate disorders and controls, with greater sensitivity over PSA. The significantly raised serum FGF-23 in prostate cancer and BPH emphasizes its involvement in BPH and prostate carcinogenesis and can be used to exclude prostatitis in cases of raised PSA levels.