Epithelial membrane antigen antibody (EMA) belongs to a heterogeneous family of highly glycosylated transmembrane proteins known as human milk fat globule (HMFG) membrane proteins. This family of antigens is not restricted to breast but may also be found in secretory epithelial cells, to a lesser degree, in non-secretory epithelium (e.g., squamous epithelium) and rarely in non-epithelial cells. EMA is best considered a broad-spectrum antibody that is reactive against many types of adenocarcinoma. Breast and skin adnexal tumors are strongly positive. A lesser degree of staining is seen in carcinomas of the endometrium, kidney, thyroid, stomach, pancreas, lung, colon, ovary, prostate and cervix. Embryonal carcinomas, medullary carcinomas of thyroid, squamous carcinomas, sarcomas, lymphomas, and melanomas all tend to be nonreactive or show rare positive cells. Transitional cell carcinomas may show weak reactivity and anaplastic large cell lymphomas can be positive for EMA.