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Introduction: The determination of epidermal growth factor receptor (EGFR) mutation status is required to guide systemic treatment in patients with non small cell lung cancer (NSCLC). Patients and methods: In this retrospective cohort, we evaluated EGFR mutational status including the resistance-associated mutation T790M using SNapShot technology combined with fragment analysis, RT PCR or NGS in the cerebrospinal fluid (CSF) of NSCLC patients diagnosed with leptomeningeal metastasis (LM) between 2012 and 2016. Results: Among 23 patients with LM (11 females), an EGFR mutation was identified in the primary tumor in 13 cases (exon 19, n=7; exon 21, n=6) at diagnosis. EGFR status was not determined in 4 cases and not interpretable in 3 cases. Other mutations included 1 KRAS mutation, 1 ALK rearrangement, and 1 HER2 mutation. At the time of molecular CSF analysis, malignant cells were observed in the CSF of 23 patients. CSF molecular analysis results were obtained for all patients. The same mutation was found in the CSF in all 13 patients with initially confirmed EGFR-mutant tumors. A L858R mutation on exon 21 was identified in the CSF in one patient where the molecular analysis of the primary tumor was not interpretable. An EGFR T790M mutation was detected in the CSF of one patient without interpretable EGFR status in the primary tumor. In another patient, a EGFR mutation was detected where no malignant cells were observed using standard cytology. Molecular blood analyses were also performed at LM diagnosis in 4 patients, with a concordance between primary tumors and CSF analysis for all 4 patients (deletion exon 19=3, no EGFR mutation=1). Initial treatments for LM from EGFR-mutant NSCLC included first- or second-generation tyrosine kinase inhibitors (TKI, n=11), chemotherapy combined with targeted therapy (n=4), chemotherapy alone (n=1), immunotherapy (n=1) and intra-CSF liposomal cytarabine combined with systemic treatment (n=9) or alone (n=2), or intraCSF MTX combined with systemic treatment (n=1). Median overall was 4.9 months (range, 0.2-39.5) in the whole population and 6 months (range, 0.2-39.5) in patients with EGFR-mutant tumors. Conclusion: A very strong concordance of EGFR mutational status (100%) was observed between primary tumor and CSF in patients with LM from NSCLC. New informations on the molecular status were obtained for 2/23 patients. These results confirm the feasibility of detection of mutations in the CSF.