We report a case of Ewing's sarcoma arising from the duodenum in a 20-year-old woman who presented with a rapidly progressive ulcerative lesion. The surgical specimen obtained via Whipple's operation revealed a small round-cell tumor (SRCT) in the first and second portion of the duodenum. The tumor cells revealed strong immunore-activity for CD 99 and vimentin and focal paranuclear dot-like immunoreactivity for cytokeratin. Electron microscopy showed primitive tumor cells with few cytoplasmic organelles, but neither neurosecretory granules nor specific cell junctions were present. On Western blot study, 68-kDa EWS/FLI1 fusion protein was detected. The occurrence of Ewing's sarcoma in the gastrointestinal hollow viscus has recently been recognized, and this case expands the known anatomic sites that can harbor Ewing's sarcoma by demonstrating primary duodenal involvement.