AbstractA case of Hand‐Schüller‐Christian disease with a nineteen year follow‐up is presented, with lesions localized to the skull and mandible. Three separate courses of irradiation therapy produced temporary recalcification of the cranial defects. A skull biopsy obtained nineteen years after onset from a recurrent skull lesion disclosed an eosinophilic granuloma. Electron microscopic examination of this tissue revealed Langerhans cell granules identical to those we had previously described in a fatal case of Letterer‐Siwe disease, and as reported in other cases of histiocytosis‐X.The findings noted in this case support Lichtenstein's thesis of a probable common etiology for the group of syndromes he has designated as histiocytosis‐X, and also add support to Lieberman's findings of relatively benign disease in the reticuloendothelioses classified as eosinophilic granuloma.