In summary, we showed that several factors contributed to SBM occurrence in NSCLC. A favorable OS correlated to a higher frequency of SBM. In addition, the presence of mutated-EGFRs predicted an increased risk for SBM independent of age and other common covariates, and was associated with a shorter MTSBM in stage IIIB-IV NSCLC patients. Furthermore, the presence of an EGFR exon19 deletion and the presence of an L858R point mutation are comparable to predict subsequent BM. These results suggest NSCLC patients with mutated-EGFRs may require a higher frequency of brain imaging assessments than those with WT-EGFR to facilitate earlier SBM detection during follow-up.