Duodenal gastrointestinal stromal tumors are rare tumors. When these tumors arise from the second part of the duodenum they can easily be misdiagnosed as a pancreatic head cancer. Case report and review of the literature. We report on a case of a 37-year-old female presenting with a one-year history of right upper quadrant pain associated with palpable abdominal tumor. Computed tomography scans showed a lesion in the head of the pancreas. No endoscopic fine-needle aspiration (FNA) cytology was carried. No specific mucosal abnormalities were reported in the duodenum. Following a roof top incision, a laparotomy was performed with an examination of the pancreas. This revealed a hard mass in the head of the pancreas and dissection in preparation for a pancreaticoduodenectomy was done. Histopathological and immunohistochemical analysis revealed the duodenal gastrointestinal stromal tumor with high-grade malignancy. Duodenal gastrointestinal stromal tumor can have a wide spectrum of clinical presentation. The accurate diagnosis of duodenal gastrointestinal stromal tumor is essential for determining the appropriate surgical intervention. In our case, a radical surgical approach was used to avoid passing near an adenocarcinoma.