Abstract： Objective To study KRAS and epidermal growth factor receptor (EGFR) mutations in primary non-small cell lung cancer (NSCLC) and their association with the effects of targeted therapy.Methods Gene mutations of KRAS and EGFR in both primary tumors and local lymph node metastases from 150 patients with NSCLC were analyzed by direct sequencing. Twelve of the patients were given gefitinib as neoadjuvant therapy after EGFR-TKI sensitive mutations had been detected in biopsies of mediastinal lymph node metastases.Results Two primary tumors and 10 metastases were identified to have KRAS mutations, while 35 primary tumors and 44 metastases were found to have EGFR mutations.KRAS and EGFR mutation status was different between primary tumors and corresponding metastases in 6.7％ (10/150) and 8.67％ (13/150) patients, respectively. One patient with no TKI sensitive mutations in the primary tumor showed disease progression with gefitinib therapy. Conclusions Our results suggest that a considerable proportion of NSCLC in Chinese patients showed discrepancy in KRAS and EGFR mutation status between primary tumors and corresponding metastases. This observation may have important implications for the use of targeted TKI therapy in the treatment of NSCLC patients.