The differential diagnostic utility of AFP, CEA, CA19.9 and TPA was evaluated in liver tumors. They were determined in the sera of 61 patients with primary hepatocellular carcinoma (HCC), 18 with secondary liver metastasis, 61 of benign liver cirrhosis in comparison to 20 normal healthy control subjects. The association of either HBV or HCV infection and HCC was also studied through the assay of HbSAg, HbSAb, and HCV-Ab. The optimal cut-off values were determined using the diagnostic accuracy measurements and the receiver operating characteristic (ROC) curves. AFP at an optimal cut-off value of 100 ng/ml and TPA at 160 U/L showed the highest sensitivity and specificity in detecting liver metastasis (100% and 87% for AFP; 100% and 54% for TPA respectively). The obtained data indicated that the combined assay of AFP and TPA resulted in a better discrimination of HCC among patients with hepatic focal lesions. HCV-Ab was detected in a higher ratio of HCC patients (83.6%) compared to HbsAg (68.9%), and both were detected in (34%) of HCC patients. This high incidence of HCV-Ab may suggest the implication of HCV in the molecular events leading to hepatic carcinogenesis.