Xanthogranulomatous cholecystitis (XGC) mimics early-stage gallbladder (GB) cancer with wall thickening on computed tomography (CT), both clinically and radiologically. Preoperative differentiation of XGC from early-stage GB cancer is important for selecting the most appropriate surgical management. Therefore, we evaluated the clinical features and multidetector CT (MDCT) findings of XGC to determine whether it can be distinguished from early-stage GB cancer. We retrospectively evaluated 25 patients with XGC and 56 patients with the wall-thickening type of T1- and T2-stage GB cancer, where all of the diagnoses were pathologically confirmed by surgical treatment. All of the patients underwent preoperative MDCT. The clinical symptoms, laboratory findings, and CT findings were compared. Abdominal pain, fever, and jaundice were noted more frequently in the patients with XGC. Serum aspartate aminotransferase and alanine aminotransferase levels were more elevated in patients with XGC, whereas carbohydrate antigen (CA 19-9) was higher in the patients with GB cancer. When the T-category cancer staging of XGC and early-stage GB cancer were compared, diffuse GB wall thickening, intramural hypoattenuated nodule, gallstone, and pericholecystic infiltration were consistent significant findings associated with XGC, regardless of the cancer staging. MDCT findings such as diffuse GB wall thickening, intramural hypoattenuated nodule, gallstone, and pericholecystic infiltration together with the clinical symptoms, can provide clues for physicians to differentiate XGC from early-stage GB cancer with wall thickening on CT.