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¹Ankara University, Faculty of Medicine, Department of Endocrinology and Metabolism, Ankara, Turkey DOI : 10.5137/1019-5149.JTN.20216-17.1 Treatment of aggressive pituitary tumors may be challenging. Temozolomide (TMZ) is a promising agent when conventional treatment methods fail. We present three patients with aggressive pituitary tumors with atypical morphology, who were resistant to conventional treatments and treated with TMZ. The first case had a somatotroph adenoma, the second a corticotroph adenoma, and the third a macroprolactinoma. We also reviewed the literature reporting TMZ efficacy in somatotroph, corticotroph and mammotroph tumors of the pituitary gland. TMZ with a schedule of 150?200 mg/m2 for 5 days every 28 days was administered to all patients. Even though only the case of macroprolactinoma had a favorable response to TMZ treatment among our patients, both radiological and hormonal recurrence occurred 30 months after the cessation of TMZ treatment. TMZ treatment was then administered again. Cases of somatotroph and corticotroph adenomas had progressed under TMZ treatment and the patients were lost due to mass effect of the tumor. A review of the literature demonstrated 67.3%, 60% and 26.7% overall response rates to TMZ treatment in prolactinoma, corticotropinoma and somatostatinoma cases, respectively. There is still a need to define response criteria uniformly to TMZ treatment in aggressive pituitary tumors. The duration of response should be reported for reliable evaluation of results. Keywords : Aggressive pituitary adenoma, Cushing"s disease, Macroprolactinoma, Somatotroph adenoma, Temozolomide