INTRODUCTION: Erdheim-Chester disease is a rare form of non-langerhans histiocytosis and its etiology is still not well established. The aims of the study were to assess the value of the bone scintigraphy and the 18F-FDG PET/CT for the diagnostic and for the latter in the therapeutic evaluation. METHODS: We retrospectively reviewed 49 patients suspected of Erdheim-Chester disease between 2004 and 2016. Bone scintigraphy was compared with histopathology and PET-CT to conventional morphological examinations and bone scintigraphy. For therapeutic evaluation, thresholds similar to PERCIST 1.0 were used. RESULTS: Forty-nine bone scintigraphy were evaluated with a sensitivity of 100%, a specificity 97%, a positive predictive value 90% and a negative predictive value of 100%. Eight patients had at least an initial PET-CT. The sensitivity compared to conventional morphological examinations differed from the location but was excellent for orbital, bone and vascular involvements. Specificity was comparable between the different examinations. Six patients treated with interferon® and three with vemurafenib® were followed by PET-CT. PET-CT, in agreement to clinicobiological data, identified 4 partial responses and one complete response with interferon® et two partial responses and one complete response with vemurafenib®. CONCLUSION: Our retrospective study suggests that bone scintigraphy and 18F-FDG PET/CT could be useful in the initial assessment of Erdheim-Chester disease but also for the latter in the therapeutic evaluation.