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Context Xanthogranulomatous inflammation commonly affects the gallbladder. To date, there have been no reports of xanthogranulomatous inflammation of the ampulla. Case report A 48-year-old female presented to us with fever, jaundice and a palpable gallbladder. Evaluation revealed features of periampullary malignancy. The patient underwent a Whipple’s pancreaticoduodenectomy. Histopathology revealed a xanthogranulomatous inflammation affecting the ampulla and the gallbladder. Conclusion Xanthogranulomatous inflammation should be added to the differential diagnosis of patients presenting with a suspected periampullary lesion accompanied by a thick-walled gallbladder.