Microadenomectomy via a transsphenoidal approach is today's treatment of choice to achieve normal cortisol blood levels in patients with ACTH-secreting pituitary tumors. Should neurosurgery fail, bilateral adrenalectomy is recommended. Today the endoscopic, transabdominal or retroperitoneal adrenalectomy is regarded as the gold standard for the operation of endocrine-active adrenal tumors. Therefore, in principle, the question of the indication for the endoscopic operation no longer arises but only the question of the technical feasibility in individual cases. We report on a patient with a pituitary-dependent Cushing's syndrome after a twice-repeated unsuccessful transsphenoidal adenomectomy and with additional polycystic kidney and liver disease, who underwent bilateral retroperitoneoscopic adrenalectomy. Despite the massive enlargement of both kidneys, it was possible to safely perform a bilateral retroperitoneoscopic adrenalectomy. In the case of marked bilateral cystic kidneys, a bilateral retroperitoneoscopic adrenalectomy in Cushing's syndrome is technical possible and a safe and effective method of treatment.