Glypican-3 (GPC3) is a glycosylphosphatidyl inositol-anchored membrane protein, which may also be found in a secreted form. Anti-GPC3 has been identified as a useful tumor marker for the diagnosis of hepatocellular carcinoma (HCC), hepatoblastoma, melanoma, testicular germ cell tumors, and Wilm’s tumor. In patients with HCC, GPC3 is overexpressed in neoplastic liver tissue and elevated in serum, but is undetectable in normal liver, benign liver, and the serum of healthy donors. GPC3 expression is 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 is also found in some types of embryonal tumors, such as Wilm’s tumor and hepatoblastoma, with a low or undetectable expression in normal adjacent tissue.