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Pituitary adenomas, namely pituitary neuroendocrine tumors (PitNETs), are a heterogeneous group of neoplasms deriving from the neuroendocrine cell of the adeno-pituitary and represent 15% of all intracranial tumors. Evidence has suggested the importance of epigenetic modifications in influencing PitNET pathophysiology and clinical behavior. Indeed, most pituitary tumors are sporadic without any specific genetic driver mutations. Furthermore, a better understanding of epigenetic modifications in PitNETs is paramount to developing novel therapeutic strategies.