Multiple pituitary hormone hypersecretions have been already described, but the combination of PRL and ACTH excess is rare. This report deals with a 42-yr-old woman affected by macroprolactinoma (PRL 12,720 microg/l, huge tumor with extrasellar extension at imaging). After one year on dopaminergic treatment causing PRL normalization and tumor shrinkage, she developed hypercortisolism (UFC 1,000 microg/24 h, ACTH 200 ng/l). Cushing's disease was diagnosed. After neurosurgery (at immunocytochemistry mixed ACTH-PRL adenoma was shown) hypercortisolism remitted, whereas pathological hyperprolactinemia with tumor remnant in cavernous sinus persisted and hypopituitarism developed. The patient reported seems atypical for the following reasons: 1) the concomitant PRL and ACTH hypersecretions; 2) the clinical presentation with hypercortisolism following hyperprolactinemia; 3) the surgical cure of hypercortisolism with persisting hyperprolactinemia.