BACKGROUND: The cervical esophagus is normally lined by squamous epithelium and is usually not exposed to gastroesophageal reflux. The aims of this study were, first, to investigate whether cardiac mucosa can be acquired in the remnant cervical esophagus after esophagectomy and cervical esophagogastrostomy and, second, to characterize this mucosa if present. METHODS: The medical records of 100 patients who had undergone esophagectomy with gastric pull-up reconstruction were studied retrospectively to identify those who had biopsies from the cervical esophagus proximal to the gastroesophageal anastomosis during postoperative follow-up. The histopathology and immunohistochemical stains were reviewed to assess similarity to Barrett's mucosa (cytokeratins [CK] 7 and 20 and DAS-1), cellular proliferation (topoisomerase 2alpha), and the potential for dysplasia (cyclo-oxygenase 2 [COX-2] and ornithine decarboxylase [ODC]). RESULTS: Supra-anastomotic biopsies were performed in 20 patients. Cardiac mucosa was present in 10 of 20 (50%) patients in whom biopsies were performed. Four patients had areas of intestinal metaplasia, and dysplasia, and adenocarcinoma developed in 1 patient. The CK7/20 and DAS-1 staining of the columnar mucosa showed a pattern similar to Barrett's mucosa. Topoisomerase 2alpha protein expression was present in 50% of patients with cardiac mucosa. DAS-1 protein was expressed in cervical columnar mucosa but not in normal squamous esophagus mucosa. The cardiac mucosa stained weakly for COX-2 and ODC. CONCLUSIONS: Cardiac mucosa can be acquired. Its expression profile is similar to cardiac mucosa and intestinal metaplasia found in Barrett's esophagus, and different from normal esophageal or gastric mucosa. The development of cardiac mucosa is likely to be related to reflux of acid into the remnant cervical esophagus as the first step in the development of Barrett's esophagus. These findings are applicable to the development of similar changes at the gastroesophageal junction.