Background Hepatocellular carcinoma (HCC) has an increasing incidence worldwide. The observation of neuroendocrine activity during the clinical course of HCC suggested the use of neuroendocrine serum markers to detect it and elevated serum chromogranin A (CgA) has been reported in patients with HCC. Aim To investigate the clinical utility of serum CgA, as a diagnostic marker of HCC. Patients and methods This studywasconductedon80patientswhowere classifiedintotwogroups.Group1: the liver cirrhosis group which included 40 patients diagnosed by clinical settings, laboratory criteria, and radiological methods. Group II: theHCCgroupwhich included 40 patients who were diagnosed by two appropriate imaging studies and serum α-fetoprotein (AFP). They were recruited from Hepatology, Gastroenterology, and Infectious Diseases Department, Benha University Hospital. Liver function tests (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and serum albumin) by colorimetric assay, CgA (by enzyme-linked immunosorbent assay), and AFP (by immunometric assay) were estimated. Results CgA levels were significantly higher in group II (HCC patients) when compared with group I (cirrhotic patients) (P