Histologic transformation from NSCLC to small-cell lung cancer (SCLC), which arises in 4–15% of cases, is a known mechanism of resistance to first-generation EGFR-TKIs that dramatically impacts patients’ prognosis, and has been reported as an important cause of resistance to osimertinib.75–79 A comprehensive understanding of the underlying mechanism(s) responsible for the histologic transformation is still missing. The gene discussed is EGFR; the disease is non-small cell lung carcinoma.