Erdheim-Chester disease is an orphan condition which involves the ongoing proliferation, migration and infiltration of the typical CD68(+), CD1a(-) histiocytes to various target foci. Consequently, both the infiltrating and fibrosing elements of the disease promote end organ damage and ultimately, failure. Presentation of the Erdheim-Chester disease typically involves longstanding diabetes insipidus in conjunction with intensifying bone pain that classically affects the femurs and tibiae. Alternatively, the disease may present with neurological deterioration of cerebellar nature. Thus, a high index of clinical suspicion is required when facing a patient with the combination of longstanding diabetes insipidus in conjunction with bone pain or cerebellar dysfunction. Typical symmetric, bilateral increased tracer uptake on a 99mTc bone scintigraphy invoLving the femurs and tibiae, is strongly suggestive of the Erdheim-Chester disease. interferon alpha is considered as the first line of treatment. Nevertheless, recent accumulated data suggests that this disease heavily relies on the Ras/Raf/MEK/ERK signal transduction pathway as inhibition of the V600E mutant BRAF by the small molecule vemurafenib among patients who are carriers of this mutation, yielded dramatic clinical responses.