Ep-CAM is a highly conserved type I transmembrane glycoprotein and is expressed on most normal and malignant epithelial cells. As a calcium-independent cell adhesion molecule, Ep-CAM is intricately linked with the Cadherin-Catenin pathway and hence the fundamental WNT pathway responsible for intracellular signaling and polarity. Ep-CAM is also known as epithelial cell adhesion molecule or MOC31, Ber-EP4. It is detected at the membrane/cytoplasm of the majority of epithelial tissues (all simple, pseudo-stratified and transitional epithelial), with the exception of the adult squamous epithelium and some epithelium-derived cells, such as hepatocytes, epidermal keratinocytes, gastric parietal cells, myoepithelial cells, and thymic cortical epithelium. In tumors, Ep-CAM is over expressed by the majority of human epithelial carcinomas, except hepatocellular carcinomas (HCC). An antibody to Ep-CAM is useful for the identification of tumors with epithelial origin, and it can also be used to differentiate HCC from metastatic adenocarcinoma in the liver.