CONTEXT: Because ectopic ACTH-secreting (EAS) tumors are often occult, improved imaging is needed. OBJECTIVE: Our objective was to evaluate the utility of [(111)In-DTPA-d-Phe]pentetreotide scintigraphy [octreotide (OCT)] imaging at 6 mCi [low OCT (LOCT)] and 18 mCi [high OCT (HOCT)], [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) and [(18)F]l-3,4-dihydroxyphenylalanine (F-DOPA)-PET scans, computed tomography (CT), and magnetic resonance imaging (MRI). DESIGN AND SETTING: The study was a prospective evaluation at a clinical research center. PATIENTS: Forty-one subjects participated, 30 (17 female) with resected EAS tumors and 11 (three female) with occult EAS, based on inferior petrosal sinus sampling results and imaging studies. INTERVENTION: INTERVENTION included CT and MRI of neck, chest, abdomen, LOCT (with or without HOCT) and FDG- or F-DOPA-PET without CT every 6-12 months. MAIN OUTCOME MEASURE: Tumor identification was the main outcome measure. RESULTS: Most recent results were analyzed. Eighteen patients had tumor resected on the first visit; otherwise, surgery occurred 33 +/- 25 (9-99) months later. Tumor size was 1.9 +/- 1.7 (0.8-8.0) cm; 83% were intrathoracic. CT, MRI, LOCT, HOCT, FDG-PET, and F-DOPA-PET had sensitivities per patient of 93% [95% confidence interval (CI) = 79-98%], 90% (95% CI = 74-96%), 57% (95% CI = 39-73%), 50% (95% CI = 25-75%), 64% (95% CI = 35-85%), and 55% (95% CI = 28-79%) and positive predictive values (PPV) per lesion of 66, 74, 79, 89, 53, and 100%, respectively. LOCT and PET detected only lesions seen by CT/MRI; abnormal LOCT or F-DOPA-PET improved PPV of CT/MRI. By modality, the fraction of patients with one or more false-positive findings was 50% by CT, 31% by MRI, 18% by L/HOCT, and 18% by FDG-PET. Eight occult EAS patients had 64 +/- 58 (9-198) months follow-up; others had none. CONCLUSIONS: High sensitivity and PPV suggest thoracic CT/MRI plus LOCT scans for initial imaging, with lesion confirmation by two modalities.