The aim of this study was to determine if cyclo-oxygenase-2 (COX-2) expression in adenocarcinoma of the esophagus affects survival outcome in patients undergoing esophagectomy. Ten patients surviving more than 3 years following an esophagectomy for adenocarcinoma of the esophagus were identified from an esophagectomy database maintained by the University of Adelaide Department of Surgery. An additional group of 10 patients, who underwent esophagectomy for adenocarcinoma, but who died within 12 months of surgery due to recurrent disease, were also identified. Pieces of the original formalin fixed carcinoma tissue embedded in paraffin blocks from all of these patients were obtained, and slices of the tumor specimens underwent immunohistochemical staining with COX-2 protein. The extent of staining was then graded by a single 'blinded' pathologist: grade 0, no staining; grade 1 +, limited staining; and grade 2 +, strong staining. Kaplan-Meier survival curves were then constructed and used to determine correlations between survival and COX-2 staining, tumor T-stage, local lymph node metastases, and tumor vascular invasion. Ninety-five percent (19/20) of patients stained positively for COX-2. Patients with grade 2 + staining had a significantly poorer survival outcome compared to grade 1 + patients (P = 0.03). There were also trends towards shorter survival with worsening T-stage, lymph node metastasis and vascular invasion. COX-2 protein appears to be expressed by most esophageal adenocarcinomas. An increased level of expression of COX-2 was associated with a poorer survival outcome in this study. COX-2 protein expression association could be a better prognostic indicator for esophageal adenocarcinoma than traditional histopathological staging.