The synchronous occurrence of a gastrointestinal stromal tumor (GIST) and pancreatic ductal adenocarcinoma (PDAC) is exceptionally rare and poses significant diagnostic and therapeutic challenges. We report a 67-year-old female presenting with biliary obstruction, right upper quadrant pain, and dyspeptic symptoms. CT imaging revealed a pancreatic head mass, while a submucosal gastric lesion was identified only intraoperatively. Laparotomy enabled excision of a pedunculated gastric GIST, whereas the unresectable pancreatic tumor involved critical vascular structures, necessitating a palliative double bypass comprising cholecystectomy, hepaticojejunostomy, gastrojejunostomy, and enteroenterostomy. Histopathology confirmed a low-risk GIST and a moderately differentiated PDAC with distinct immunohistochemical profiles, supporting the presence of two independent primary tumors.

This case underscores the critical importance of meticulous intraoperative exploration, particularly in the presence of atypical or incidentally discovered lesions, and demonstrates the durable palliation afforded by surgical bypass in unresectable PDAC. Beyond the clinical context, potential molecular overlaps—activation of MAPK/ERK and PI3K/AKT/mTOR pathways, VEGF-mediated angiogenesis, and defects in DNA repair—provide a plausible biological basis for the synchronous occurrence of these otherwise unrelated neoplasms, informing potential strategies for personalized therapy