Gefitinib is the first approved epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who failed to respond to conventional chemotherapy. Gefitinib has fairly effective anti-tumour activity in patients with tumours harboring EGFR gene mutations. However, there has been no data about the preoperative gefitinib treatment in NSCLC patients. We reported here two cases of surgical resection of residual disease after dramatic response to gefitinib in patients with lung adenocarcinoma harboring EGFR gene mutation. Because both of our patients initially had advanced local tumour burden (bulky N2 disease), complete resection would not have been technically feasible. However, preoperative gefitinib treatment made it possible to achieve complete resection in both patients. We believe that clinical trials are required to evaluate the role of preoperative treatment of EGFR-TKIs in patients with locally advanced NSCLC harboring EGFR gene mutation.