Fever of unknown origin (FUO) is an uncommon disease, and its underlying etiology may include a number causes, i.e., infections, malignancies, autoimmune conditions. Diagnosis is often a difficult task, and usually physician spend time and money in order to define the etiology of FUO. We report a case of patient who presented with FUO and headache, and positron emission tomography (PET) with 2-deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG) allowed to reveal the presence of a large vessel vasculitis. 18F-FDG PET may represent an useful tool in patients with FUO, since it can early depict an hypermetabolic activity due to inflammation and so help to achieve a final diagnosis in some cases of FUO.