Interdigitating dendritic cell sarcoma is an extremely rare malignancy derived from antigen-presenting cells. Dendritic cells constitute a heterogeneous group of cells, which includes Langerhans cells, dermal dendrocytes, follicular dendritic cells, and interdigitating dendritic cells present in lymphoid and nonlymphoid organs. We report the case of a 36-year-old woman who presented with epigastric pain, projectile vomiting, and significant weight loss. Upper gastrointestinal endoscopy showed a duodenal lesion; a biopsy of the lesion was taken and was diagnosed as sarcoma. She underwent a Whipple procedure. A final diagnosis of interdigitating dendritic cell sarcoma was made, with liver and peripancreatic lymph node involvement. The patient deteriorated rapidly and died 4 months later. Although interdigitating dendritic cell sarcoma of the duodenum is extremely rare, we think it should be included in the differential diagnosis of unusual spindle cell tumors with a rich lymphocytic infiltrate.