CONTEXT: Ectopic Cushing's Syndrome (ECS) can be a diagnostic challenge with the hormonal source difficult to find. This study analyzes the accuracy of imaging studies in ECS localization. EVIDENCE ACQUISITION: Systematic review of medical literature for ECS case series providing individual patient data on at least one conventional imaging technique (computed tomography [CT]/magnetic resonance imaging) and one of the following: 111In-pentetreotide (OCT), 131I/123I-metaiodobenzylguanidine, 18Ffluoro-2-deoxyglucose-positron emission tomography (FDG-PET), 18F-fluorodopa-PET (F-DOPA-PET), 68Ga- DOTATATE-PET/CT or 68Ga-DOTATOC-PET/CT scan (68Gallium-SSTR-PET/CT). EVIDENCE SUMMARY: The analysis comprised 231 patients (females, 50.2%; age, 42.617 y). Overall, 52.4%(121/231) had "overt" ECS,18.6% had "occult" ECS, and 29% had "covert" ECS. Tumors were located in the lung (55.3%), mediastinum-thymus (7.9%), pancreas (8.5%), adrenal glands (6.4%), gastrointestinal tract (5.4%), thyroid (3.7%), and other sites (12.8%), and primary tumors were mostly bronchial neuroendocrine tumors (NETs) (54.8%), pancreatic NETs (8%), mediastinum-thymus NETs (6.9%), gastrointestinal NETs (5.3%), pheochromocytoma (6.4%), neuroblastoma (3.2%), and medullary thyroid carcinoma (3.2%). Tumors were localized byCTin66.2%(137/207), magnetic resonance imaging in 51.5% (53/103), OCT in 48.9% (84/172), FDG-PET in 51.7% (46/89), F-DOPAPET in 57.1% (12/21), 131/123I-metaiodobenzylguanidine in 30.8% (4/13), and 68Gallium-SSTRPET/CT in 81.8% (18/22) of cases. Molecular imaging discovered 79.1% (53/67) of tumors unidentified by conventional radiology, with OCT the most commonly used, revealing the tumor in 64%, followed by FDG-PET in 59.4%. F-DOPA-PET was used in only seven covert cases (sensitivity, 85.7%). Notably, 68Gallium-SSTR-PET/CT had 100% sensitivity among covert cases. CONCLUSIONS: Nuclear medicine improves the sensitivity of conventional radiology when tumor site identification is problematic. OCT offers a good availability/reliability ratio, and FDG-PET was proven useful. 68Gallium-SSTR-PET/CT use was infrequent, despite offering the highest sensitivity.