Reduced expression of E-cadherin, a cell-cell adhesion molecule, was frequently observed in several types of human carcinomas, and the protein plays a role as an invasion suppressor in vitro. In an attempt to evaluate the significance of E-cadherin gene in non-small cell lung cancer (NSCLC), we undertook the immunohistochemical and molecule structural analyses of E-cadherin gene in 40 resection specimens of NSCLC and the corresponding paracarcinoma controls. E-cadherin expression was explored by immunohistochemistry with a monoclonal antibody, and the E-cadherin gene was studied by polymerase chain reaction single-strand conformation polymorphism analysis (PCR-SSCP). The analysis represented in this study demonstrated clear reduction in the expression of E-cadherin proteins in the cancer tissues. However, only in one amplicon were aberrant bands detected, which was a single polymorphic site (codon 692; exon 13), and no somatic mutation was found. These results indicated that defected E-cadherin expression might play a role in the development of malignant phenotype in NSCLC, even though the genetic mutation of E-cadherin gene is not involved in the pathogenesis of NSCLC and does not appear to be direct cause for the reduced expression of E-cadherin gene.