Betacellulin (BTC), a member of the epidermal growth factor (EGF) family, was originally identified as a growth-promoting factor in the conditioned medium of a mouse pancreatic-cell carcinoma (insulinoma) cell line and has since been identified in humans. BTC is synthesized as a large transmembrane precursor molecule that can be cleaved proteolytically to release the soluble form of BTC or function as membrane-anchored growth factors in juxtacrine signaling. BTC, in addition to stimulating homodimers of ErbB-1 and ErbB-4, is capable of binding and activating all possible combinations of heterodimeric ErbB receptors including the oncogenic ErbB-2/ErbB-3 complex. BTC is also expressed in some human malignancies and may have an important role in tumor growth progression.