Tumors of the head and neck region form a heterogeneous group of pathologies, including various benign lesions and malignant neoplasms. Endoglin, also known as CD105, is an accessory receptor for transforming growth factor beta (TGF-β), that regulates angiogenesis, both under physiological and pathological conditions. It is highly expressed in proliferating endothelial cells. Therefore, it is considered as a marker of tumor-related angiogenesis. In this review we discuss the role of endoglin as a possible marker of carcinogenesis, as well as a potential target for antibody-based therapies in the neoplasms of the head and neck region.