The 9C4 monoclonal antibody specifically binds to human epithelial cell adhesion molecule (EpCAM), also known as adenocarcinoma associated antigen and CD326. EpCAM is an approximately 40-kDa type 1 transmembrane glycoprotein and adhesion molecule that mediates intercellular interactions via homotypic adhesion. The epithelial cells present in non-squamous epithelia and tumors derived from such cells show EpCAM expression. Tumors arising from non-epithelial cells, such as lymphoma, mesothelioma, neuroblastoma, and melanoma, do not express EpCAM. The normal epithelial cells reactive with anti-EpCAM antibodies are those present in the (lower) respiratory tract; the (lower) gastrointestinal tract; tubules in the kidney; the surface epithelium of the ovary; the exocrine and endocrine pancreas; secondary germ cells of telogenic hair follicles; and secretory tubules of sweat glands in the skin, whereas the epidermis is negative. In addition, all epithelial cells in the thyroid and epithelial cells in the thymus show EpCAM expression, while the outer cortex and Hassall's corpuscles have low expression. EpCAM is expressed on a variety of stem and progenitor cells, and its down-regulation is associated with decreased proliferation and differentiation toward endoderm and mesoderm lineages.