After about 20 years of exciting improvements in treatment efficacy outcomes of advanced epidermal growth factor receptor (<i>EGFR</i>) mutant and anaplastic lymphoma kinase (<i>ALK</i>) rearranged non-small cell lung cancer (NSCLC), also combined with a progressively better safety profile, from chemotherapy to new generation tyrosine kinase inhibitors (TKIs) (osimertinib, alectinib, brigatinib), the recent MARIPOSA and CROWN trials have changed this trend. The gene discussed is EGFR; the disease is non-small cell lung carcinoma.