SCLC transformation is 1 resistance mechanism associated with first-generation EGFR-TKIs, and is more frequent in lung adenocarcinomas with EGFR-activating mutations than in EGFR wild-type tumors.[7–9] A number of mechanisms of acquired resistance to EGFR-TKI therapy in EGFR-mutant lung adenocarcinoma have been described, including the EGFR T790M mutation, EGFR amplification, MET gene amplification, PIK3CA mutation, and transformation to SCLC.[10,11] However, the potential mechanism underlying SCLC phenotype conversion after TKI therapy remains unclear. The gene discussed is PIK3CA; the disease is lung adenocarcinoma.