Pituitary carcinomas are extremely rare (< 0.2% of pituitary tumors) and most commonly arise from longstanding, recurrent, and invasive prolactinomas and ACTH-secreting macroadenomas. Pituitary carcinoma is defined by the presence of a pituitary tumor that either (1) is noncontiguous with the primary sellar tumor, or 2) has spread to distant sites, such as spinal lesions, lymph nodes, bones, or liver. Multimodal therapy with surgery, radiation, and systemic therapy is often required. For patients with symptomatic mass effects, palliative surgical debulking followed by radiation therapy is usually recommended. In addition, TMZ, an orally-active alkylating agent, has proven efficacy as monotherapy in pituitary carcinomas. A positive response to TMZ has been associated with a downregulation of the DNA-repair enzyme O 6 -methylguanine-DNA methyltransferase (MGMT), although variable methods of MGMT quantitation limit its current utility. Lastly, the diagnosis of pituitary carcinoma carries a poor prognosis, with a mean survival of < 4 years.