Although rare, EGFR L833V/H835L in cis mutation represents a biologically oncogenic and clinically actionable variant in NSCLC.<h4>Significance</h4>Our study reveals the rare EGFR L833V/H835L cis mutation as an aggressive oncogenic driver in lung adenocarcinoma, highly responsive to EGFR-directed therapy. This evidence concerns the gene EGFR and lung adenocarcinoma.