BACKGROUND: Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract and occur rarely in the duodenum. Splenic angiosarcoma is an aggressive neoplasm with an extremely poor prognosis. METHODS: We report a case of a 70-year-old man hospitalized for abdominal pain in the upper quadrants, dyspepsia and nausea, previously treated for Hodgkin lymphoma 30 years ago. Abdominal CT showed a solid nodular lesion in the third portion of the duodenum, the presence of retropancreatic, aortic and caval lymph nodes, and four nodular splenic masses. 111In-octreotide scintigraphy revealed pathological tissue accumulation in the duodenal region, and in the retropancreatic, retroduodenal, aortic and caval lymph nodes, suggesting a nonfunctioning neuroendocrine peripancreatic tumor. RESULTS: At exploratory laparotomy, an exophytic soft tumor was found originating from the third portion of the duodenum. Pancreas-preserving duodenectomy with duodenojejunostomy, splenectomy and lymphnodectomy of retropancreatic aortic and caval lymph nodes were performed. Pathological evaluation and immunohistochemical studies showed the presence of a duodenal gastrointestinal stromal tumor with low mitotic activity and a well-differentiated angiosarcoma localized to the spleen and invading lymph nodes. CONCLUSIONS: We speculated that the angiosarcoma and duodenal gastrointestinal stromal tumors of this patient were due to the treatment of Hodgkin lymphoma with radiotherapy 30 years ago. Pancreas-preserving segmental duodenectomy can be used to treat non-malignant neoplasms of the duodenum and avoid extensive surgery. Splenectomy is the treatment of choice for localized angiosarcomas but a strict follow-up is mandatory because of the possibility of recurrence. © 2012, Hepatobiliary Pancreat Dis Int.