The ErbB3/HER3 receptor protein is known to play critical roles in normal mammalian development and is potentially involved in the genesis and progression of human cancers. Unique among the four members of the ErbB/HER receptor subfamily, the ErbB3 protein is devoid of intrinsic protein tyrosine kinase activity, yet can recruit intracellular signaling molecules that elicit cell proliferation and transformation. In vitro studies have begun to elucidate the mechanisms by which the ErbB3 protein, in cooperation with other ErbB family coreceptors, is activated by the binding of its several polypeptide ligands, is phosphorylated in the context of coreceptor complexes, and subsequently activates signaling cascades in the cell. The transforming potential of the ErbB3/HER3 gene has been characterized via its ectopic expression in model cultured cell systems, and its involvement in the etiology of human cancers has been suggested by studies of ErbB3/HER3 expression in a number of tumor types. The roles of the ErbB3 receptor protein in mammalian embryological development have recently been illuminated by targeted disruption of the ErbB3/HER3 gene in mouse.