A meta-analysis was performed to determine EGFR mutations, gene amplification, and protein expression and KRAS mutations in primary and metastatic nonsmall cell lung cancer (NSCLC). We found that KRAS gene mutation frequencies were higher in primary than in metastatic tumors. There was no significant difference in EGFR mutation frequency between the primary and metastatic tumors. These results suggest that KRAS mutations in primary NSCLC foci may be a more accurate biomarker than in metastases to reflect KRAS mutation status. Combined detection of EGFR and KRAS mutations in primary NSCLC foci appears to be an optimal approach for first-line EGFR-TKI therapy.