The burden of prostate cancer is high globally and especially among men of African descent. Serum prostate specific antigen(PSA) has long been used for diagnosis,however,its low specificity and indiscriminate use has led to unnecessary biopsies,over-diagnosis and over treatment of apparently indolent tumours.This weakness of PSA as a biomarker for cancer prostate has necessitated the search and identification of an alternative to it. To compare the sensitivity, specificity, positive predictive value, and negative predictive value of serum Microseminoprotein-beta(MSMB) with serum total prostate specific antigen (tPSA) in the diagnosis of prostate cancer in African men. This is a 12-month prospective study of patients aged 50 years and above with lower urinary tract symptoms (LUTS), PSA greater than 4ng/ml and/or abnormal digital rectal examination, leading to the suspicion of prostate cancer. Patients with a histological diagnosis of prostate cancer formed the study group while those with negative biopsy/benign prostatic hyperplasia on histology served as the control group.All had detailed history and focused examination with serum levels of Microseminoproteinbeta(MSMB) and total PSA (tPSA) determined using Enzyme-linked immunosorbent assay methods. Data were analyzed using SPSS version 20.0 for windows. The mean age of patients with prostate cancer and those with benign prostatic hyperplasia (BPH)/negative biopsy was 67.40 ± 9.08 and 65.43 ± 9.68 years, with an age range of 50-91 and 50-89 years, respectively. Compared to MSMB, tPSA had a higher sensitivity (82.5 vs 57.5%), specificity (77.5 vs 30.0%), PPV (78.6 vs 45.1), NPV (81.6 vs 41.4%) and diagnostic accuracy (80.6 vs 43.8%). Serum total PSA had a higher validity than serum MSMB in diagnosing prostate cancer. Hence, tPSA remains a relevant serum tumour biomarker in diagnosing prostate cancer in our urological practice.