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Perivascular epithelial cell tumors (PEComas) of the pancreas are rare mesenchymal tumors and, to our knowledge, only 20 cases have been reported to date.We report a 43-year-old female who presented with upper abdominal pain for 1 year. She underwent an exploratory laparotomy at a local hospital, which failed to resect the tumor. Five months later, she came to the Chinese National Cancer Center for surgery. Preoperative imaging revealed an 11.5-cm-sized mass located in the head of the pancreas. At the microscopic level, the tumor was composed of epithelioid and spindle cells possessing clear to focally granular eosinophilic cytoplasm, which grew in a nested and alveolar pattern around blood vessels. The tumor cells showed immunoreactivity for human melanoma black 45 (HMB-45), but did not express epithelial or endocrine markers.Pancreatic PEComa.Pancreaticoduodenectomy, partial hepatectomy, and vascular replacement were performed. After the surgery, the patient received 4 cycles of chemotherapy.The patient is free of recurrence and metastasis 1.5 years after surgical resection.PEComa should be recognized as a preoperative differential diagnosis of pancreatic tumors. For treatment, removal of the tumor should be attempted, and in the case of tumors with malignant tendencies, the addition of chemotherapy should be considered.