Erdheim-Chester's disease is a non-inherited multi-focal lipid-storing histiocytosis of unknown origin without a complete and convincing diagnostic and therapeutic protocol. We have previously suggested diagnostic methods using radioisotopes to evaluate this disseminating disease, but they are neither specific nor selective in this regard. The present hypothesis-driven paper reviewing our case proposes novel approaches involving nuclear medicine and utilizing radiopharmaceuticals to identify this potentially fatal multi-system disease.