Decreased expression of tumor suppressor gene PTEN has been reported to be a poor prognostic indicator in a variety of human malignant tumors. The purpose of this study was to clarify the roles of PTEN in esophageal squamous cell carcinoma (ESCC) and the prognostic significance of PTEN protein expression. Sixty-four patients from a high incidence area of northern China who underwent esophagectomy for ESCC between January 1998 and December 1999 enrolled in this study. PTEN expression was assessed by immunohistochemistry in 64 primary cancers and 64 paired normal esophageal epithelium tissues. The positive rate and staining grade of PTEN protein expression was lower in the esophageal cancers than in paired adjacent normal esophageal epithelium (P < 0.001). PTEN expression correlated with tumor differentiation (P = 0.001), tumor infiltration depth (P = 0.015) and pTNM staging (P = 0.048). The 5-year survival rate in patients with PTEN positive expression was 82% compared to 39% in patients with PTEN negative expression (P = 0.0019). Our results show that the expression of PTEN is decreased in ESCC compared to normal esophageal epithelium. Therefore, PTEN may play an important role in carcinogenesis and the progression of ESCC in a high incidence area of northern China, and PTEN could serve as an important factor to predict clinical outcome and prognosis.