First-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) could induce dramatic tumor responses in non-small-cell lung cancer patients with EGFR-activating mutations. However, a small proportion of patients have no tumor response on initial EGFR TKI treatment with an activating EGFR mutation and the primary resistance mechanism is not well understood. Here, we report the patient with primary dual MET/EGFR mutation treated with icotinib shows a disease progression, but the chest computed tomography shows the mass has significantly shrunk after 3 weeks of single-agent crizotinib. These suggest that de novo MET amplification could be a potential mechanism of intrinsic resistance to first-generation EGFR TKI.