Rationale: Mutations in epidermal growth factor receptor (EGFR) play critical roles in the pathogenesis of non-small cell lung cancer (NSCLC), and they are highly associated with sensitivity to tyrosine kinase inhibitors. Targeted therapies are approved for patients with "classical" mutations and a small number of other mutations. However, patients with rare, even double EGFR mutations have different responses to EGFR tyrosine kinase inhibitor, which brings uncertainty to clinical practice. Patient concerns: A 74-year-old woman, never-smoker, was presented with chest pain. Chest computed tomography scan showed a big lesion in the right upper lobe with mediastinal lymph nodes metastases. Fine-needle biopsy and pathology suggested lung adenocarcinoma. A rare G719A/L833V double mutation of EGFR was detected in both tissue and plasma samples by next-generation sequencing. Interventions and outcomes: Icotinib was used as first-line therapy and showed good efficacy. Partial response was achieved, and the progression-free survival was 8 months. Lessons: This is the first report of the icotinib treatment achieving long-lasting and stable disease control in an NSCLC patient with EGFR G719A/L833V mutation. Icotinib could be a first-line treatment option in NSCLC patients harboring EGFR G719A/L833V mutation.