Abstract: Objective:Mutations in epidermal growth factor receptor (EGFR) can predict tumor response to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). However, not all cases of NSCLC with EGFR mutations can respond well; thus, discovering the heterogeneity of NSCLC at the molecular level is necessary. This study aimed to determine the discrepancy in EGFR mutations in primary tumors, N 2 lymph nodes, and plasma samples. Methods:Primary tumors, N 2 lymph nodes, and plasma samples obtained from 49patients with stage ⅢA-N2 NSCLC were analyzed for EGFR mutations in exons 19and 21by using mutant-enriched liquidchip technology. Results: In 49patients, we detected18(36. 7% ) EGFR mutations in primary tumors,11(22. 4% ) mutations in N2 lymph nodes, and 2 (4. 1%) mutations in plasma samples. Eleven (22. 4%) cases showed discordance in EGFR mutations between primary tu-mors and N 2 lymph nodes. In nine cases, EGFR mutations were detected only in primary tumors, whereas EGFR mutations were de -tected only in N 2 lymph nodes in two cases. In addition, EGFR mutations were detected in the plasma samples of two patients, who al -so carry mutations in their primary tumors. Conclusion: A considerable proportion of NSCLC cases showed discrepancy in EGFR muta-tions between primary tumors and N 2 lymph nodes. In addition, the detection rate of EGFR mutations was lower in plasma samples obtained from patients with stage IIIA-N2 NSCLC. All of the results indicated tumor heterogeneity at the molecular level during metas-tasis, and this heterogeneity may have implications during treatment with TKIs.