Thickening of the gallbladder wall is often associated with acute or chronic cholecystitis, adenomyomatosis and gallbladder carcinoma or seen in the context of liver and systemic diseases (acute hepatitis, cirrhosis, sepsis). Here we present a case of a 61 y.o. man with focal thickening of the gallbladder wall, in whom all imaging techniques were inconclusive. Pathological examination of the resected gallbladder revealed acute-on-chronic cholecystitis. We describe focal acute cholecystitis in absence of the classic clinical and imaging findings (Murphy's sign, fever, gallstones, hydrops, pericholecystic fluid) and mimicking a gallbladder carcinoma.