Erdheim-Chester disease (ECD), first described by Jakob Erdheim and William Chester in 1930, is a rare form of non-Langerhan's cell histiocytosis with unknown aetiology, is charaterized by systemic xanthogranulomatous infiltrative disease. To date, about 350 cases of ECD have been described in the medical literature. The typical ECD diagnostic triad is bone pain, diabetes insipidus and bilateral exophthalmos. A 24 years old man came at our attention for polydipsia with nocturnal and diurnal polyuria, anorexia, febrile episodes (38(o)C), and arthromyalgia especially in the knees. Physical examination showed bilateral periorbital xanthelasma. Blood exams showed increase of plasma osmolarity, haematocrit, sodium and urea and decrease of potassium. Urine exams showed just decreased urine specific gravity, (1.001;normal range: 1.010-1.030) suggestive for central diabetes insipidus (CDI). Brain magnetic resonance with gadolinium enhancement showed the presence of multiple hyperintense lesions expecially in neurohypophysis (swollen and with markedly contrast enhancement). All these data raised the suspision of neurosarcoidosis, so a chest and abdomen contrast enhancement computed tomography was performed, which didn't show abnormalities, making less possible the diagnosis of sarcoidosis. Two weeks later, whole-body (from head to pelvis) plus lower limbs 18-fluorine-labelled 2-deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) was performed. Uptake of (18)F-FDG was observed in the upper portion of the midbrain area (SUV(max) 7.1) and the pituitary gland (SUV(max) 7.3), and diffuse bone marrow uptake of (18)F-FDG in the proximal epiphysis and metaphysis of both humeri and thigh bones (SUV(max) 6.5), shoulder blades, pelvis bones and the L2 vertebral body (SUV(max) 3.9). This (18)F-FDG PET/CT confirmed the presence of brain lesion seen in MRI , the absence of visceral lesions, but also showed the presence of an atypical bone uptake of (18)F-FDG, leading to the suspision of ECD. A technetium-99m-methyl-diphosphonate skeletal scintigraphy ((99m)Tc-MDP) scan showed diffuse uptake of the radiopharmaceutical, in the diaphysis of long bones and in the left portion of the body and the spinous process of L2. Considering the difficulties of an osteomedullary or brain biopsy, biopsy was performed on a right anterior thoracic cutaneous xanthelasma. Histology showed lipid-laden histiocytes (CD1a-, CD68+, S-100 protein -) with small nuclei, Touton giant, lymphocytic infiltrates, eosinophils and fibrosis, ECD gold standard patterns as reported in literature. The patient was discharged with the diagnosis of ECD with central nervous system (CNS) manifestations, and treatment started. The diagnosis can be lead by the most charateristic bone findings of symmetrical osteosclerosis of the long bones, especially the lower limbs (tibia and fibula), involving metaphyses and diaphyses but sparing epiphyses. The typical pattern of osteoscerosis of the long bones reflects increased osteoblastic activity. About half of all ECD patients may experience extraskeletal manifestations, including CNS. Visceral involvement in ECD is not specific, and this enforces the diagnostic value of skeletal imaging findings. Furthermore xanthomas can be found at any location on the skin, especially the eyelids as in our patient. For visceral involvement, CT is most useful, while MRI is more sensitive for CNS lesions. Involvement of CNS may be frequently revealed clinically by diabetes insipidus. Few case reports have shown that (18)F-FDG PET/CT scanning could be useful in assessing the extension of ECD lesions. Both radiography and (99m)Tc-MDP skeletal scintigraphy may reveal osteosclerosis of the long bones, which is a typical finding in ECD. The typical bone pattern of (18)F-FDG PET/CT scan is specific for ECD and (99m)Tc-MDP skeletal scintigraphy may be performed in patients in whom initial (18)F-FDG PET/CT scans present the possibility of ECD diagnosis. Others reported that (18)F-FDG PET/CT scans had good sensitivity (66.7%) and specificity (92.3%) as compared with MRI of the CNS involvement or lesions. In conclusion, the (18)F-FDG PET/CT scan and the (99m)Tc-MDP scan depicted many of the most relevant lesions of ECD for the initial assessment of ECD in our patient.