Abstract Background and objective : The ectopic ACTH syndrome (EAS) is a heterogeneous condition, caused by neuroendocrine neoplasms (NEN) located in the lungs, thymus or pancreas. Our purpose was to evaluate the long-term outcome of these patients. Design : Retrospective study at a referral center. Methods: The charts of 164 patients with Cushing syndrome, followed at our center from 1993 to 2019 were analyzed. Results : EAS was found in 16 patients (9.75%, 9 women, mean age 36.01 years), who had been followed for a median of 72 months. The source of EAS was a NEN in 10 patients (8 bronchial and 2 thymic carcinoid tumors) and a mixed corticomedullary tumor, consisting of a pheochromocytoma and an adrenocortical carcinoma in one patient. In two of the 6 patients initially considered to have occult EAS, the source of the ACTH excess became apparent after adrenalectomy, whereas in the remaining 4 (25%) it has remained occult. Of the 11 patients in whom resection of the NEN was attempted, 10 patients achieved an early remission (91%) but 4 (25%) of these had a recurrence during follow up (biochemically and clinically silent in 2). Three patients have died (18.75%): the young woman with the mixed corticomedullary tumor, a man with a thymic NEN that evolved into a neuroendocrine (NE) carcinoma after 11 years of follow up and a woman with a bronchial NEN. Conclusions : The course of EAS varies according to tumor type and grade. Some patients have a protracted course whereas others may evolve into NE carcinomas.