E-cadherin, a calcium-dependent cell-cell adhesion molecule, functions as maintenance of epithelial integrity. nm23, encoded by non-metastatic 23 gene, plays a key role in differentiation of many kinds of epithelium. Loss or dysfunction of E-cadherin and nm23 was frequently identified in many types of human cancers and is considered to correlate with invasive/metastatic phenotype. We previously reported that defective expression of E-cadherin might play a role in the development of the malignant phenotype in non-small cell lung cancer (NSCLC) [Q.Y. Fei, H.T. Zhang, X.F. Chen, et al., Defected expression of Ecadherin in non-small cell lung cancer, Lung Cancer 37 (2002) 147-152]. In an attempt to evaluate the significance of E-cadherin and nm23 in human non-small cell lung cancer, we performed mRNA expression and genetic structure analyses of the E-cadherin and nm23 genes in 54 NSCLCs and 46 normal lung tissues. The mRNA expression was determined by semi-quantitative RT-PCR, and genetic structure was examined through PCR-SSCP followed by sequencing. Although no mutation of the E-cadherin and nm23 genes was detected, the results obtained in the present study showed that reduction of E-cadherin and nm23 mRNA expression remarkably correlated with low histological differentiation, increasing stage as well as lymph node metastases (P<0.05). These data provide us with support for the idea that dysfunction of E-cadherin and nm23 has a role in progression of NSCLC and that the examination of E-cadherin and nm23 expression can provide experimental evidence for clinical treatment.