Limited number of studies have been reported regarding the utilization of F-18-fluoro-deoxy-glucose (F-18-FDG) positron emission tomography/computed tomography (F-18-FDG PET/CT) in Langerhans cell histiocytosis (LCH). The aim of this study was to assess the role of F-18-FDG PET/CT in the diagnosis and treatment of LCH. Methods Eight newly diagnosed and seven recurrent patients with LCH received F-18-FDG PET/CT scans. The diagnosis of LCH was established by pathology, multi-modality imaging, and clinical follow-up. Results F-18-FDG PET/CT was positive in 14 patients with 13 true positives and one false positive. All 45 LCH lesions were F-18-FDG avid including six small bone lesions <1.0 cm in diameter. The mean maximal standardized uptake value (SUVmax) was 7.13 +/- 4.91. F-18-FDG uptake showed no significant difference between newly diagnosed lesions vs recurrent lesions (SUVmax: 6.50 +/- 2.97 vs. 7.93 +/- 6.60, t=-0.901, P=0.376). Among 45 LCH lesions, 68.9% (31/45) were found in bones and 31.1% (14/45) in soft tissue. The most commonly involved bones were the pelvis and vertebrae. There was no significant difference in F-18-FDG uptake between bone lesions vs. non-bone lesions (SUVmax: 6.30 +/- 2.87 vs. 8.97 +/- 7.58, t=1.277, P=0.221). In two patients, changes in F-18-FDG uptake on serial PET/CT scans reflected response of lesions to treatment. Conclusions The present study suggests that F-18-FDG PET/CT may be useful for diagnosis and assessing the treatment response of LCH. Because of the small sample size, further research is warranted to confirm our findings.