A submucosal tumor was resected endoscopically from the duodenal bulb in a 43-year-old man complaining of epigastric discomfort. The tumor, measuring 22 x 20 x 19mm, consisted mainly of Brunner's glands with no atypia. However, close histologic examination disclosed a focus of glands with cellular and structural atypia. The atypical glands showed staining by periodic acid-Schiff, alcian blue, and high iron-diamine methods. Mucin histochemistry was examined, and the atypical glands resembled the excretory ducts rather than the acinar cells of the tumor. Immunohistochemically, positivity for MIB-1 was high (38.0%), and p53-positive cells were detected sporadically in the atypical glands. These results indicated that the atypical glands probably represented a neoplastic lesion. Brunner's gland adenomas associated with foci of true neoplasm are very rare; only two cases, including one patient with microcarcinoid tumors, have been reported.