In summary, our data show that in the NSCLC EGFR‐targeted therapy setting, analysing the presence and dynamics of both actionable oncogenic drivers (such as EGFR mutations) and other, potentially “non‐actionable” alterations (such as TP53 mutations and global copy number changes), before and during treatment, can offer clinically relevant information to potentially guide subsequent clinical management. The gene discussed is EGFR; the disease is non-small cell lung carcinoma.