Pyloric gland adenoma is a recently described and very rare entity. The occurrence of adenoma is very unusual in Barrett's epithelium of the esophagus. We report a case of esophageal polyp showing the features of pyloric gland adenoma, which was surrounded by so-called specialized columnar epithelium. Immunohistochemically, most tumor glands were strongly positive for MUC6, except in the superficial layer. MUC5AC was positive in almost all tumor cells, but MUC2 and CD10 were negative in the tumor. MIB-1-positive proliferating cells were distributed throughout the tumor. Microdissection and comparative genomic hybridization analyses revealed losses on 2p24-25.2, 2q14.1-ter, 5q31.3-32, 6q23-24, 8q23-24.2, 11q22.3-24 and 18q21.1-22. This is the first case of pyloric gland adenoma found to arise in Barrett's epithelium of the esophagus, showing its unstable and precancerous nature.