The advent of new diagnostic procedures such as petrosal venous sampling and CRF testing has improved the possibilities of precise location of the site of hormonal overproduction in Cushing's syndrome. We report on a case of ectopic ACTH-dependent Cushing's syndrome in which the use of such techniques helped to locate the tumor. A 45-year-old woman with definite ACTH-dependent Cushing's syndrome was referred to our clinic for evaluation. ACTH, cortisol and urinary 17OHCS failed to suppress on high dose dexamethasone oral administration. Computerized tomography showed bilateral adrenal hyperplasia and an empty sella turcica. ACTH and cortisol did not increase after CRF administration. Staged caval system catheterism via both femoral veins up to the inferior petrosal sinuses, including after CRF administration, demonstrated no ACTH gradient between staged samples and simultaneous peripheral venous blood. This suggested a tumor drained by the portal system. An abdominal ultrasonography demonstrated a pancreatic mass, that was surgically excised and appeared as a benign islet cell tumor. Portal vein ACTH promptly decreased after tumor excision and postoperative peripheral cortisol and ACTH were normal. On immunostaining the tumor cells proved to be positive for ACTH.