Brain metastases (BM) occur in 20-40% of patients with non-small cell lung cancer (NSCLC) at some point during the disease course . NSCLC is heterogeneous in terms of its histological subtypes and distinct driving oncogenes , which may affect the development of BM. Adenocarcinoma histology has been reported to be associated with BM from NSCLC. Epidermal growth factor receptor (EGFR) is one of the most common oncogenes, activating mutations of which drive tumor growth in NSCLC. The association between the EGFR mutation status and BM in patients with NSCLC has been noted in the past [3–6]. However, these findings have not been consistently observed. It is unclear whether the EGFR mutation status can predict the occurrence of subsequent BM (SBM) in advanced NSCLC or whether the high frequency of BM in EGFR-mutated NSCLC can be mainly attributed to the survival factor of EGFR mutations. Moreover, the rationales behind the above findings are not well determined. In addition, evidence suggests that EGFR exon 19 deletion-positive NSCLC is distinct from EGFR exon 21 (L858R) point mutation-positive NSCLC with regard to the tumor response to treatment and patient survival [7–10]. Nonetheless, the question regarding whether these two common subtypes of EGFR mutations have different impacts on the occurrence of BM in NSCLC has not been well addressed.