Mucoepidermoid carcinoma (MEC) of lung is a rare malignancy of lung which originates from minor salivary glands of tracheobronchial tree. EGFR targeted therapy by inhibition of EGFR activation with the specific tyrosine kinase inhibitors (TKIs) has shown meaningful anti-tumor activity in patients with EGFR TK mutation and/or amplification, or in patients with adenocarcinoma. In the present study, we find that MEC has EGFR mutation in 40% (2 out of 5) of cases, and all mutations are L858R mutation. In addition, we also observed that a MEC patient well-responded to EGFR TKI in the absence of EGFR mutation or amplification. These data indicate for the first time that MEC of lung is another potential target of EGFR inhibitor, and more extended clinical investigation is warranted.