EGFR and ERBBs have been implicated in the progression of various types of cancer through regulation of cell proliferation, survival, migration, angiogenesis, tumorigenesis, and metastasis by binding with ligands including epidermal growth factor (EGF), heparin-binding EGF-like growth factor (HB-EGF), transforming growth factor-α (TGFα), and β-cellulin as high-affinity ligands, in addition to amphiregulin (AREG), epiregulin (EREG), or epigen (EPGN) as low-affinity ligands [7,8]. This evidence concerns the gene HBEGF and cancer.