Background: Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) is a soft tissue malignancy arising from the neuroectoderm. While the locations of these extraskeletal manifestations are diverse, origin from the small bowel and small bowel mesentery is extremely rare. Intra-abdominal manifestations of ES/PNETs are nonspecific, and patients present with a wide range of symptoms, most frequently vague abdominal pain. Case Report: A 66-year-old female initially presented with vague and nonspecific symptoms of hypotension, anemia, dyspnea, and coffee-ground emesis. Imaging workup with computed tomography and fluorodeoxyglucose positron emission tomography demonstrated a metabolically active large mass involving the duodenum and measuring 10.3 × 8.8 × 12.3 cm. The mass was characterized as an ES/PNET on histopathologic diagnosis. The patient was treated with chemotherapy followed by radical resection and was disease-free at 1 year postpresentation. Conclusion: This case highlights that while ES/PNETs are rare tumors of the abdomen, they should be considered in cases of large soft tissue masses in patients presenting with nonspecific symptoms. To the best of our knowledge, this case is the fourth report in the literature of an ES/PNET involving the duodenum.

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