Although there are several precedents of cancers evolving from oncogene dependence to independence [including small cell transformation in EGFR-mutant NSCLC and ABL kinase–independent imatinib resistance in chronic myelogenous leukemia (44, 45)], we characterize here a subset of cancer that exhibits a switch in dependence to another oncogene while retaining expression and activation of the original driver oncogene. The gene discussed is EGFR; the disease is non-small cell lung carcinoma.