Gallbladder disease is a very common condition that encompasses a heterogeneous group of diseases with a wide range of severity and clinical manifestations. Gallbladder disorders include biliary colic, acute cholecystitis, chronic cholecystitis, choledocholithiasis, Mirizzi syndrome, and gallstone ileus. We report the case of a 70-year-old man who presented to the emergency department complaining of worsening abdominal pain, located in the right upper quadrant and radiating to the right shoulder. It was aggravated by food intake and relieved with the use of antacid medications. The medical history of the patient was significant for stable angina, hypertension, diabetes mellitus, hyperlipidemia, and sickle cell trait. Examination of the abdomen revealed generalized tenderness with guarding. Abdominal computed tomography scan demonstrated the presence of significant diffuse thickening of the gallbladder wall with poor contrast enhancement. Complete resection of the gallbladder was performed because of suspected gallbladder carcinoma. Histopathological examination revealed xanthogranulomatous cholecystitis, which is a rare form of chronic cholecystitis. The differentiation between gallbladder carcinoma and xanthogranulomatous cholecystitis may not be easy and histopathological examination is the most accurate way to make the diagnosis.