The aim of this exploratory retrospective analysis was to explore whether deep molecular profiling using whole exome sequencing (WES) of tumor tissue at initial diagnosis could facilitate a more reliable prediction of the subsequent development of EGFR p.T790M for patients with EGFR mutated NSCLC receiving first‐/second‐generation EGFR TKI as the first‐line therapy. Here, EGFR is linked to non-small cell lung carcinoma.