Background <p>Rhabdomyosarcoma is a rare type of soft-tissue sarcoma that is more frequently observed in children and is less common in adults. Rhabdomyosarcoma can occur in any part of the body, including tissues without skeletal muscles. The main subtypes of rhabdomyosarcoma are embryonal, alveolar, and pleomorphic. Pleomorphic rhabdomyosarcoma is a rare variant typically found in adults over 45 years old and is characterized by early metastasis.</p> Case presentation <p>This article reports a rare case of primary pleomorphic rhabdomyosarcoma in the duodenum of A 67-year-old Iranian male. The patient presented to the hospital with epigastric pain and severe anemia. Abdominal imaging revealed a polypoid mass in the duodenum and antropyloric region of the stomach. Laboratory tests confirmed severe anemia, and an endoscopic biopsy initially misdiagnosed the mass as a poorly differentiated epithelioid gastrointestinal stromal tumor.</p> Conclusion <p>Following surgery and comprehensive immunohistochemical analysis, the final diagnosis of primary pleomorphic rhabdomyosarcoma in the duodenum was confirmed. This case highlights the diagnostic challenges associated with pleomorphic rhabdomyosarcoma in the gastrointestinal tract and underscores the importance of comprehensive immunohistochemical analysis for accurate diagnosis. The article emphasizes the need for further research to better understand the clinical behavior and optimal management of primary gastrointestinal pleomorphic rhabdomyosarcoma.</p>