Erdheim-Chester disease is a non-Langerhans cell histiocytosis, classically thought to be rare, but diagnosed more frequently nowadays (250 published cases). Histiocytes of Erdheim-Chester disease are positive for CD68 but not for CD1a, contrary to Langerhans cell histiocytosis. Two signs highly evocative of this diagnosis are nearly constant tracer uptake by the long bones on (99)Tc bone scintigraphy and a "hairy kidney" appearance on abdominal CT scan. A more "elegant" diagnostic method is ultrasound-guided biopsy of the perirenal infiltration. Cardiovascular involvement, which affects the aorta ("coated aorta") as well as all the cardiac layers, leads to one third of the deaths related to this disease. Central nervous system infiltration (especially cerebellar) is severe and difficult to treat. The prognosis is extremely variable and is often worse when there is a cardiovascular and/or central nervous system involvement. The treatment, decided upon on a case-by-case basis at a specialist center, often begins with interferon alpha.