Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis characterized by progressive histiocytic proliferation with multiorgan involvement, typically of the kidney, skin, brain, and lung, and less frequently, the heart and retro-orbital tissue. Fluorine-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) plays an important role in the management of this disease. It has been reported that FDG PET imaging allows accurate evaluation of the extent of the disease at baseline, as well as assessment of response to any specific therapy. In this case, a 57-year-old Chinese man presented with functional decline and a urinary tract infection. He had a prior history of xanthogranulomas of bilateral canthal masses. On imaging, he was found to have left hydronephrosis, diffuse urothelial thickening, increased density of the perinephric fat, mural thickening of the descending aorta and soft tissue masses along the posterior wall of the right atrium extending into the region of the interatrial septum and involving the right atrioventricular groove. Histopathology revealed retroperitoneal fibrosis. An IV contrast-enhanced FDG PET scan showed increased activity in a previously unidentified brain stem mass and the shafts of bilateral femora. Varying levels of FDG uptake were seen in the other lesions.