Non-small cell lung carcinoma is a leading cause of cancer-related death. Amplification of the two oncogenes MET and SOX2 is frequently encountered in non-small-cell lung carcinoma. This study aimed to use real-time quantitative PCR to assess the correlation of MET and SOX2 amplification with clinicopathological factors. This study was conducted using 115 tissue samples including 57 squamous cell carcinomas (SCCs), 50 adenocarcinomas (ADCs) and 8 adenosquamous carcinomas (ADSCs). A total of 67 patients (58.3%) had a history of smoking. Our results showed that the frequency of MET amplification in SCCs was significantly higher compared to ADCs (χ(2)=8.0, P=0.005). SOX2 showed a markedly preferential amplification in SCCs compared to ADCs in the smoking group cases (P=0.014). Lymph node invasion correlated with MET amplification in SCCs marginally more significantly compared to ADCs (P=0.02). The amplified MET occurred more frequently in SCCs compared to ADCs correlated to tumor dimension at a small scale (<5 cm) (P=0.01). No significant difference in SOX2 amplification was found with regards to lymph node metastasis or tumor dimension. SOX2 and MET amplifications were not associated with gender or age. However, MET amplification in SCCs among patients younger than 64 years of age was higher compared to ADCs and ADSCs (P=0.03). Among ADSCs, MET was not amplified among patients who had never been smokers or were younger than 64 years of age. Neither MET nor SOX2 were amplified in tumors with dimensions <5 cm and without lymph node invasion. Findings of this study showed that MET and SOX2 amplifications are more common in the SCCs of smokers. Moreover, MET amplification is intrinsic in SCCs particularly among smokers, with regards to tumor growth, lymph node invasion and negative correlation to SOX2 amplification. The incidence of discrepancy in the amplifications of MET and SOX2 in SCCs and ADCs suggests that the MET and SOX2 genes play different roles in SCC and ADC tumorigenesis, respectively, particularly among smokers.