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This study aimed to present a proper understanding of the fluorine-18-fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) value in localizing the primary lesion in adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome in a relatively large case cohort.This retrospective study included 47 patients with ACTH-dependent Cushing syndrome, who underwent an 18F-FDG PET/CT examination in our hospital from November 2010 to January 2018. The serum cortisol, 24 h urine cortisol, serum ACTH, and high-dose dexamethasone suppression test were measured in all the patients. Bilateral inferior petrosal sinus sampling was performed in 28/47 patients. Pituitary magnetic resonance imaging and whole-body 18F-FDG PET/CT were performed in all patients.Serum ACTH at 8 a.m. higher than 161.8 pg/ml as the cut-off value showed the best diagnostic accuracy (73.9%) for the successful localization of the primary lesions. In Cushing disease patients, the pituitary maximum standardized uptake value 18F-FDG PET/CT (n=11) did not show significant differences compared with that in ectopic ACTH syndrome (EAS) patients (n=20). In terms of EAS, the descending order of maximum standardized uptake value was 13.2±8.3 (4.8–26.4) in pancreatic neuroendocrine tumors (n=4), 7.1±2.4 (3.5–10.1) in mediastinal carcinoid (n=11), and 2.0±0.1 (1.9–2.2) in bronchial carcinoid (n=4). This study first reported the 18F-FDG PET/CT images of ACTH-secreting olfactory neuroblastoma.Serum ACTH level determines the success rate of localization of the primary ACTH-secreting tumor in ACTH-dependent syndrome. 18F-FDG PET/CT plays a role in localizing the site for EAS, although it plays a limited role in Cushing disease.