The aim of this study was to investigate the correlation between Wnt1/beta-catenin expression and the clinicopathologic features and prognosis of patients with esophageal squamous cell carcinoma (ESCC). The mRNA and protein expression levels of Wnt1/beta-catenin genes in 70 ESCC and 15 adjacent noncancerous paraffin-embedded samples were determined by real-time quantitative polymerase chain reaction and immunohistochemical staining. The mRNA expression level of Wnt1/beta-catenin in ESCC was significantly higher than that in the adjacent noncancerous tissues (1.9934 +/- 1.9888 vs. 0.8863 +/- 0.665, p = 0.0184; 0.2854 +/- 0.1298 vs. 0.0128 +/- 0.0158, p = 0.0000, respectively), and the overexpression of Wnt1/beta-catenin mRNA was aggressively associated with lymph node metastasis and advanced pathological stage (p < 0.0001). The protein expression level of Wnt1/beta-catenin was also significantly higher than that in the adjacent noncancerous tissues (0.3830 +/- 0.0947 vs. 0.2721 +/- 0.1474, p = 0.0002; 0.2835 +/- 0.0844 vs. 0.2352 +/- 0.0670, p = 0.0210, respectively); however, the overexpression was not associated with clinicopathologic characteristics. Meanwhile, the protein expression level of Wnt1 had no relevance with that of beta-catenin. The overexpression of Wnt1/beta-catenin might be an important molecular marker to predict the clinicopathologic stage and prognosis of ESCC, and the level of Wnt1/beta-catenin mRNA was conversely correlated with lymph node metastasis and advanced pathological stage. The overexpression of Wnt1/beta-catenin mRNA should also predict poor prognosis of ESCC; however, it might not be an independent prognostic factor.