Abstract The expression of epidermal growth factor receptor (EGFr) and transforming growth factor alpha (TGF-α) was compared with the presence of “squamous differentiation” (SD) visualized in various histotypes of endometrial carcinoma by using a panel of monoclonal antibodies. The results of the current study demonstrate that EGFr and TGF-α are present in routinely processed endometrial carcinoma. The highest positive EGFr and TGF-α expression was seen in the group of adenocarcinomas with SD. The more intense EGFr and TGF-α immunoreactivity was observed in “squamous” foci both in adenoacanthomas (AA) and in adenosquamous carcinomas (AS). These EGFr- and TGF-α-positive squamous areas prevalently displayed a “stratification-related” cytokeratin (CK) immunoprofile characterized by the expression of CKs 1, 4, 5, 10, 13, 14, and 16. No correlation was found between EGFr- and TGF-α-positive status and depth of myometrial invasion or surgical stage. These results clearly demonstrate that EGFr and TGF-α expression is related remarkably to endometrial carcinoma with “squamous” areas both morphologically and immunophenotypically. This specific association leads us to suggest that EGFr and TGF-α expression in endometrial carcinoma may be prevalently involved in the equilibrium of cell differentiation of the “squamous” foci commonly observed in this group of neoplasias.