EGFR and neoplasm: In such circumstances, tumor rebiopsy is recommended as a second line therapy, especially after the failure of first or second generation EGFR TKIs.[1] Two main types of resistance mechanisms to EGFR mutated NSCLC are “on target” and “off target” resistance.[2] The former is the secondary alteration in the target oncogene, including either a second site mutation that promotes TKI resistance or the amplification or loss of the targeted oncogene.