Disregarded for several years largely because of the absence of detectable ErbB3 mutations in cancer samples and for the lack of a functional kinase domain in its intra-cytoplasmic region, ErbB3 is instead one of the most potent activators of the PI3K/Akt axis and is upregulated and trans-phosphorylated in several forms of cancer, in particular following treatment with EGFR and HER2 inhibitors. The gene discussed is EGFR; the disease is cancer.