BACKGROUND: Considerable overlap exists in the value of total prostate specific antigen (tPSA) in both prostate cancer (Pca) and benign prostate hyperplasia (BPH). Developing an effective biochemical screening test that will complement PSA assay could reduce the associated cost of care and give timely attention to prostate cancer patients even when they are still asymptomatic is therefore desirable. This work was therefore an attempt to evaluate the possible roles of lipids, antioxidants, and trace metals in breaking the diagnostic tie between Pca and BPH. MATERIALS AND METHODS: Anthropometric characteristics, total prostate specific antigen (tPSA), serum lipids (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides), Vit. E, total antioxidant status (TAS), and trace metals (Se, Cu, Fe, Zn, and Mn) were determined in 40 patients with histopathological diagnosis of BPH and Pca. Forty age matched control subjects were also recruited from the same community. Informed consent was obtained from all the participants in the study. A P-value < 0.05 was considered significant. RESULTS: There were significant variations in the weight, hip circumference, and body mass index (BMI) across the group but the post hoc test did not show any difference between patients with prostate cancer and BPH. Among the biochemical parameters studied, only the total cholesterol and triglyceride differed significantly between patients with BPH and prostate cancer patients. Cut-offs from ROC for BPH and prostate cancer at 88.9 sensitivity and 66.7% specificity (95% CI) were 88.5 mg and 161 mg/dl for triglycerides and cholesterol respectively. Furthermore there were no significant variations in the mean levels of copper and tPSA, Vit E, and LDL cholesterol among the study subjects and the controls. CONCLUSION: Prior to prostate biopsy, serum lipid (especially, fasting triglycerides, total cholesterol) could help in early discrimination of patients with BPH from prostate cancer in adjunct to total PSA and other management protocol for diagnosis of prostate cancer. The use of trace metal or antioxidants may have limited advantages. Further studies in this regard will be very desirable to see if this pattern of triglyceride and total cholesterol values in BPH and Pca are sustainable.