Erdheim-Chester disease is an uncommon non-Langerhans cell histiocytosis with systemic manifestations. Most cases discuss radiologic findings once a pathologic diagnosis has already been established. We describe a patient with symptoms and no previously known diagnosis who was imaged with computed tomography, magnetic resonance imaging, and positron emission tomography. This case is unusual in that radiologic imaging demonstrated interatrial septum and diffuse cardiac involvement, in addition to the other characteristic lesions of Erdheim-Chester disease. The importance of this case to the radiologist is the expansion of the differential diagnosis of processes involving the interatrial septum and retroperitoneum.