EGFR-mutant NSCLC is characterized by tumor heterogeneity that, under treatment pressure, may lead to the emergence of tumor clones with additional genetic alterations including MET or HER2 amplification, PIK3CA mutations, or with histological transformation to small cell lung cancer (SCLC) and the epithelial-to-mesenchymal transition (EMT). Here, PIK3CA is linked to small cell lung carcinoma.