C-reactive protein (CRP) is a prototype acute phase protein which has been known to be synthesized in hepatocytes. Although serum elevation of CRP has been reported to be an indicator of the unfavorable outcome of the patients in some malignant tumors, the expression of the protein in carcinoma cells has not been investigated. The aim of the current study was to assess the immunohistochemical expression of CRP in squamous cell carcinoma (SCC) of the esophagus and to find its biological significance. Immunohistochemical examination for CRP expression was performed for 37 advanced esophageal SCCs with the depth of T2, T3 or T4, which had been surgically resected without preoperative therapy for the patients. Eighteen carcinomas (48.6%) demonstrated immunohistochemical CRP expression. Univariate analysis showed that the prognosis of the patients with esophageal SCCs expressing CRP was significantly worse than that in patients with tumors without CRP expression (P=0.017). Moreover, CRP expression was found to be an independent prognosticator in patients with esophageal SCCs in the multivariate analysis (P=0.036). To the best of authors' knowledge, this is the first report that demonstrated the possible carcinoma-related expression of CRP in SCCs of the esophagus and its biological significance as the prognosticator of the patients.