We present a 68-year-old male patient with an exceptionally aggressive tumour which invaded to the skull base, cavernous sinus, nasopharynx, sphenoid sinus, pituitary fossa, bilateral parasellar regions, premedullary cistern, and left infratemporal fossa. Headache was the only symptom. The serum prolactin level was 95,973 ng/ml. The patient was treated by right subfrontal craniotomy with removal of the tumour. Because it did not respond well to surgical treatment and the electron micrograph showed abundant secretory granules in some parts of the specimen, post-operative radiotherapy and bromocriptine therapy were instituted. After combined therapies and a long-term follow-up, only little residual pituitary tumour was seen with serum prolactin progressively dropped to 717 ng/ml with no obvious symptoms. The histological findings, the ideal treatments and the clinical course of multi-invasive giant prolactinoma will be discussed.