The epidermal growth factor receptor (EGFR) gene product is a receptor tyrosine kinase (TK) that affects many important downstream pathways. The recent finding that mutations in EGFR predict the response of lung cancers to therapies that target the TK domain of the gene product has generated considerable interest. The mutations are associated with adenocarcinoma histology, oriental origin, female gender and never-smoker status. Most mutations target structures in the TK domain that appear to be essential for the phosphorylation function of the gene. Cancer cells with mutant EGFR genes might become physiologically dependent on the continued activity of the gene for the maintenance of their malignant phenotype; however, this might also be a target for therapy.