Interference with the activation of growth factor receptors, specifically epidermal growth factor receptor (EGFR) and/or other member(s) of its family (human epidermal growth factor [HER]-2, -3 and -4) represents a promising strategy for development of novel and selective anticancer therapies. Indeed, a number of inhibitors that target either EGFR or HER-2, but not both, have been developed for treatment of epithelial cancers. However, since most solid tumors express different EGFRs, identification of inhibitor(s) targeting multiple EGFR family members may provide a therapeutic benefit to a broader patient population. To this end, the author proposes that EGFR-related protein (ERRP), a recently isolated negative regulator of EGFR that possesses a substantial homology to the extracellular ligand-binding domain of EGFR and its family members, is a pan-ErbB inhibitor that targets multiple members of the EGFR family. This review discusses the significance of EbB [corrected] family of receptors in epithelial cancers, and describes isolation, characterization and the mechanisms of action of ERRP as well as its potential application as a therapeutic agent for a wide variety of epithelial cancers.