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The identification of intestinal metaplasia (IM) in the esophagus is necessary for the selection of patients with Barrett esophagus (BE) for surveillance. We studied 108 esophageal biopsy and resection specimens, clinically diagnosed as BE, and stained them for CDX2, villin, HepPar-1, and cytokeratin (CK) 7 to investigate sensitivity for identifying IM. H&E-stained sections showed definite goblet cells in 94 cases. CDX2 and villin were positive in all 94 cases. Of 38 cardia- and 9 fundic-type mucosa samples associated with BE, 13 (34%) and 0 (0%) displayed CDX2 positivity and 21 (55%) and 1 (11%) displayed villin positivity, respectively. HepPar-1 was positive in 54 (57%) of 94 cases with IM and negative in the associated cardia- and fundic-type mucosa. A full-thickness CK7 staining pattern was present in 90 (96%) of samples with IM and 22 (58%) and 0 (0%) of the associated cardia- and fundic-type mucosa, respectively. None of 20 control samples of morphologically normal gastric mucosa stained for CDX2 or villin. CDX2 and villin are sensitive markers for early-stage IM and can supplement the histologic identification of this premalignant condition in the esophagus.