Xanthogranulomatous inflammation is an uncommon, though well-recognized entity that has been described in various organs but mostly commonly in the kidney and gallbladder. There have been few reports of its occurrence in the appendix. We report a 39-year-old man who presented with fever, right lower quadrant abdominal pain and mass. Abdominal computed tomography (CT) revealed diffuse wall thickening over the terminal ileum and cecum with involvement of the mesentery. CT-guided biopsy showed colitis with infiltration of lymphocytes, neutrophils and eosinophils. The patient's illness responded to intravenous antibiotics, but relapsed after switching to oral antibiotics. After the second course of intravenous antibiotics was given without resolution of symptoms, exploratory laparotomy was performed. Although operative findings favored colitis of the cecum, cancer of the cecum could not be completely ruled out. Right hemicolectomy was done and pathology confirmed the diagnosis of xanthogranulomatous appendicitis. This case illustrates that xanthogranulomatous appendicitis may mimic a locally advanced cancer, has a benign course, and can be cured by surgical resection.