The epidermal growth factor receptor (EGFR) is over-expressed in various human epithelial tumors usually due to the gene amplification. EGFR gene amplification in tumors frequently contain its rearrangements and among them, the most common extracellular domain mutation is receptor variant III, EGFRvIII (also known as de2-7EGFR or DEGFR). The molecular mass of EGFRvIII is approximately 145 kDa and this genetic change of tumor-specific mutation results from a deletion of 267 amino acids spanning exons 2-7 of the EGFR gene. These consequences make the variant EGFRvIII incapable of binding known ligand. It is expressed in a majority of patients with glioblastoma multiforme. And the evidence shows aberrant EGFRvIII signaling is important for driving tumor progression. HER3 (Human epidermal growth factor receptor 3), also referred to ERBB3, ErbB-3, LCCS2, Erb-b2 receptor tyrosine kinase 3 or receptor tyrosine-protein kinase erbB-3, is a membrane-bound protein with a neuregulin binding domain (not an active kinase domain). It is encoded by the human ERBB3 gene mapping at the chromosome 12q13.2. HER3 acts as a cell surface receptor for neuregulins and belongs to the epidermal growth factor receptor (EGFR/ERBB) family of receptor tyrosine kinase. Regulation of HER3 expressions and signal transductions involve many interacting proteins, including PI3K, Shc, Nrdp1, and E3 ubiquitin ligases NEDD4. Overexpression of this gene has been reported in various cancers, such as bladder, prostate, and breast tumors. This receptor is emerging as a molecule target for increasing cancers.