We studied the expression of axin and beta-catenin and their relation to clinicopathologic factors in 100 non-small cell lung cancers (NSCLCs) by immunohistochemical analysis. The mutation in exon 3 of the beta-catenin gene was examined by polymerase chain reaction and direct sequencing. Preserved axin expression was significantly higher in well- and moderately differentiated NSCLC samples than in poorly differentiated ones. Reduced membranous expression of beta-catenin was shown in 80 cases, whereas 26 cases had aberrant nuclear expression. Poor differentiation and lymph node metastasis were associated significantly with reduced beta-catenin expression. Lower axin expression was related significantly to higher nuclear beta-catenin expression. However, this study failed to detect any exon 3 mutation in the beta-catenin gene in the 100 NSCLC samples. We conclude that reduced beta-catenin and axin expression might predict poor differentiation in NSCLC. Reduced axin expression, but not mutation in exon 3, might be an important explanation for the abnormal beta-catenin expression in NSCLC.