Our findings that pre-treatment EGFR T790M mutation was significantly associated with brain metastasis in patients with EGFR-mutated tumors receiving first- or second-generation EGFR-TKIs suggested that therapeutically targeting the pre-existing minor subpopulation harboring T790M mutation may have the advantage of preventing the development of brain metastasis in NSCLC. Here, EGFR is linked to non-small cell lung carcinoma.