We report a case of a 60-year-old female diagnosed with epidermal growth factor receptor (EGFR) exon 19-mutant non-small cell lung cancer (NSCLC). She developed leptomeningeal disease (LMD) about 2 years after her initial cancer diagnosis and experienced multiple subsequent relapses of her leptomeningeal carcinomatosis with parenchymal brain metastases. She currently is alive with excellent performance status at 82 months since the LMD diagnosis. Treatment has consisted of different conventional and experimental EGFR targeted therapies along with intrathecal chemotherapy. This report, to the best of our knowledge, represents the longest overall survival (OS) of LMD reported in patients with EGFR-mutant NSCLC and suggests that leveraging different mechanisms of action to target EGFR mutation in a sequential fashion with multidisciplinary teams’ involvement can potentially help control the LMD and prolong the OS in this patient population.