Leptomeningeal metastasis (LM) is a disastrous complication of advanced lung adenocarcinoma (LAC) associated with poor prognosis and rapid deterioration of performance status. The prevalence of epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) co-alterations in patients with LAC was low. Herein, we report a patient with alterations in both EGFR (p. G719A+L747V) and echinoderm microtubule-associated protein-like ALK (EML4-ALK) fusion and LM who was treated with afatinib. The patient's clinical symptoms improved, and imaging examination revealed reduced intracranial and extracranial lesions. The progression-free survival (PFS) using afatinib for LM was 25 months, and no severe adverse events occurred.