Objective: Xanthogranulomatous cholecystitis (XGC) is a rare but recognized variant of chronic cholecystitis, characterized by severe proliferation of fibrous tissue and accumulation of lipid-laden macrophages in areas of destructive inflammation. It is significant as clinico-radiologically it can be confused with the prognostically far more serious condition of carcinoma of the gallbladder. The aim was to evaluate the clinicopathological, pre- and intraoperative findings of XGC and also correlate the mucosal response of XGC with various gallstone parameters. Materials and Methods: In this retrospective 6-year study, 33 XGC (24 women and 9 men; mean age, 48.2 years) cases from 630 cholecystectomies were studied. Results: Cholelithiasis and a thickened gallbladder wall were the most frequent findings both radiologically and intraoperatively. Grossly the gallbladders were normal sized, fibrosed, or enlarged. Xanthogranulomatous nodules were yellowish, single, or multiple, raised above the surface, irregular, and frequently involved the fundus and body (24 cases). A combined stone was a common association (26 cases), mostly solitary and large (≥1 cm). Microscopically, in 24 cases, xanthogranulomatous foci were centered around Rokitansky–Aschoff sinuses and confined to the gallbladder wall, whereas larger diffuse destructive tumor-like masses occupied the full thickness of the gallbladder wall (9 cases) with variable extension into the adjacent fat, connective tissue, and surrounding structures, mainly liver. In four patients, carcinoma of the gallbladder could not be excluded either radiologically or intraoperatively, and were definitively diagnosed histologically as XGC. Conclusions: The correct diagnosis of XGC remains a challenge in medical practice and definitive diagnosis depends exclusively on histopathologic examination. Our study was an effort to contribute toward better understanding of this histopathologic entity.