Mutations of epithelial growth factor receptor (EGFR) in exon 19 and 21 are both believed to be associated with carcinogenesis, sensitivity to tyrosine kinase drugs and with the prognosis of non-small cell lung cancers (NSCLCs). However, their exact clinical significance remains disputable. We detected the mutations of 157 NSCLCs from mainland China with high resolution melting analysis and identified exon mutations with DNA sequencing. Of the 157 cases examined, 57 displayed EGFR mutations which included 22 in exon 19 and 35 in exon 21. Current research has shown that EGFR mutations are more commonly associated with the female population and East Asians, with additional significance being adenocarcinomas. Our current findings are supporting this sugestion. We analysed the clinicalpathological characteristics of mutations in exon 19 and 21 separately, which showed that the mutation frequency of NSCLCs in exon 21, but not in exon 19, were significantly higher in females. Comparatively, mutation frequencies in exon 19 were significantly higher in the stage I and II than in the stage III abnd IV, while tumors with lymph node metastasis and the stage III and IV demonstrated significantly higher mutation frequencies in exon 21. Additionally, exon mutations in the left and right lung showed significant differences: with exon 19 mutations being more frequent in the tumors of left lung, and exon 21 mutuations showing a higher incidence in right lung tumors. This suggests that, in mainland China, NSCLCs with EGFR mutations in exon 19 could have a less malignant character than those with mutations in exon 21. It's the first report that EGFR mutations in exon 19 and exon 21 in NSCLC patients may relate to the tumor sites, but further research is still required.