Erdheim-Chester disease is a very rare xanthogranulomatous, non-Langerhans cell systemic histiocytosis with an unknown etiology and pathogenesis. Histologically, it is characterized by a diffuse infiltration with large, foamy histiocytes, rare Touton-like giant cells, lymphocytic aggregates, and fibrosis. The histiocytes differ from the Langerhans cell group in ontogenesis, immunohistochemistry (positive for CD68 and negative for CD1a and S100 protein), and ultrastructural appearance (lack of Birbeck granules). Although most of the cases have symmetric osteosclerosis of the long bones, an involvement of the axial skeleton has also been described. Extraskeletal lesions are present in more than 50% of the patients and may involve the retroperitoneal space, lungs, kidneys, brain, retro-orbital space, and heart. This study presents the case of a patient with Erdheim-Chester disease with vertebral destruction and, for the first time, to our knowledge, involvement of the liver. The diagnosis is based on radiologic, histologic, immunohistochemical, and ultrastructural findings.