Pituitary carcinomas are rare, making up some 0.2% of all pituitary tumors, but represent a particular challenge to clin- ical practice. The diagnosis of a pituitary carcinoma requires evidence of metastatic disease, either outside the central ner- vous system (CNS) or as separate noncontiguous foci within the CNS. They may present as typical pituitary adenomas, which reveal their malignant character only as time progresses, or as peculiarly aggressive tumors ab initio. Re- centchangesinhistopathologicalclassificationhaveclarified many of the features of such tumors, including immunohis- tochemical staining for Ki-67 and p53, but to date none has been found to be pathognomonic. The majority of carcinomas are secretory, usually arising from corticotroph tumors or prolactinomas, but all histological types and secretory pat- terns are represented. Treatment is by surgery, transsphe- noidal wherever possible, and conventional and stereotactic radiotherapy, but ultimately, a plethora of therapies may be required,includingvariousattemptsatmedicaltherapy.Che- motherapy in some instances probably prolongs survival, but, ingeneral,theirprogressfromthediagnosisofcarcinomatous changes is progressive and inexorable. However, we do not believe there will be any real prospect of long-term survival untilthedevelopmentanduseoftherapiestargetedatspecific molecular abnormalities. (J Clin Endocrinol Metab 90: 3089-3099, 2005)