Hepatocellular carcinoma (HCC) is one of the most commonmalignancies worldwide and it is one of the major causes of death, because ofits high frequency and poor prognosis. HCC is now a rather commonmalignancy in Egypt which usually develops on top of liver cirrhosissecondary to viral infection.The aim of this study was to investigate the potential role ofChromogranin-A (Cg-A) as a diagnostic non invasive marker in HCCpatients with or without Alpha-fetoprotein (AFP) elevation in order to add adiagnostic beneficial value in patients with low levels of AFP and suspectedto have HCC.This study was conducted on 60 cirrhotic patients, 30 of themdocumented HCC using Triphasic CT and histopathological assessment and30 with no evidence of HCC; as well as 30 normal healthy subjects serving ascontrol group.We determined the level of AFP, Cg-A for all cases together withhistory taking, clinical examination, liver biochemical profile, viral markers,conventional US, abdominal Triphasic CT and guided liver biopsy for HCCcases with atypical CT pattern.We concluded that the diagnostic sensitivity of AFP at a cutoff 200ng/ml was 32.2% and the specificity 100%. The cutoff level of Cg-A fordiagnosis of HCC in this study was 16.75 nmol/l, with a sensitivity andspecificity 66.7% and 80% respectively. Serum Cg-A was significantlyelevated in the HCC group having focal hepatic lesions >2 cm in diameterwhen compared to those lesions <2 cm. The combined use of the two markers(AFP and Cg-A) led to increase the sensitivity of AFP from 60% to 93.3%.This showed that simultaneous measurements of serum AFP and Cg-A fordetecting HCC may give the highest index of detection.