We found that, independent of the survival factor, the presence of mutated-EGFRs was significantly associated with an increased risk of SBM in NSCLC as compared to those with WT-EGFR (HR = 2.98, P = 0.002). Similar results were recently reported by other research groups [4, 20, 21]. More importantly, we further observed that the lung tumors with mutated-EGFR progressed to the brain more rapidly than those with WT-EGFR in terms of MTSBM (23.5 months vs. NR, P = 0.017). These findings imply that the biological traits in cancer cells may contribute to SBM occurrence in NSCLC, however this possibility was rarely investigated in previous clinical reports. Prior in vitro experiments showed that the activation of EGFR upon ligand stimulation or by the mutation of EGFRvIII rather than EGFR overexpression correlates with cell migration and invasion in epithelial cancer cell lines, such as breast, oral squamous and glioblastoma cancers, and in NIH3T3 fibroblasts [11–13, 22]. Herein, we showed that the presence of mutated-EGFRs in lung cancer cells enhances cell mobility and promotes vimentin protein, a hallmark of mesenchymal cells . Obviously, in vitro data in the current study were not robust and had limitations to indicate the presence of epithelial-to-mesenchymal transition (EMT). However, the additional analyses of tumor samples from our and others’ cohorts supported the correlation of EGFR-mutation status with vimentin expression, suggesting that EGFR-mutation status may be prone to undergo EMT-mediated cancer cell dissemination.