Glypican-3 (GPC3) is a glycosylphospatidyl inositol-anchored membrane protein, which may also be found in a secreted form. Recently, GPC3 was identified to be useful tumor marker for the diagnosis of HCC, hepatoblastoma, melanoma, testicular germ cell tumors, and Wilms tumor. In patients with HCC, GPC3 was overexpressed in neoplastic liver tissue and elevated in serum but was undetectable in normal liver, benign liver, and the serum of healthy donors. GPC3 expression was also found to be higher in HCC liver tissue than in cirrhotic liver or liver with focal lesions such as dysplastic nodules and areas of hepatic adenoma (HA) with malignant transformation. In the context of testicular germ cell tumors, GPC3 expression is up-regulated in certain histologic subtypes, specifically yolk sac tumors and choriocarcinoma. A high level of GPC3 expression has also been found in some types of embryonal tumors, such as Wilms tumor and hepatoblastoma, with a low or undetectable expression in normal adjacent tissue. Together these studies indicate that GPC3 is an important tumor marker.