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Objective: Despite pituitary neuroendocrine tumor (PitNET) being extra‐axial tumors without direct damage to brain tissue, patients with PitNET exhibit neuropsychological impairments. However, it remains unclear whether there are neuropsychological differences between PitNET and intra‐axial tumors that directly destroy the brain parenchyma. This prospective study aims to clarify this distinction to inform decision‐making for intracranial tumors of diverse origins. Methods: A total of 146 patients with PitNET, 74 patients with glioma representing intra‐axial tumors, and 52 age‐, sex‐, and education‐matched healthy controls were recruited. All patients received standard treatment and postoperative rehabilitation. Clinical data were meticulously collected, and neuropsychological tests were administered to all participants both before and 3 months after surgery. Results: Both PitNET and glioma patients experience the dual burden of cognitive and affective deficits. However, the feature of these deficits differs substantially. In PitNET patients, the deficits are relatively mild and focal, whereas in glioma patients, they are severe and extensive. Specifically, PitNET patients exhibit deficits in memory, anxiety, and negative affect. In contrast, glioma patients display deficits in executive function, attention, anxiety, positive/negative affect, and empathy. Notably, except for persistent memory deficits, the majority of neuropsychological scores declines in PitNET patients are restorable and can reach improvement within a short period after standard surgical therapy and perioperative management. Conversely, glioma patients not only fail to show improvements but also demonstrate worsening in terms of general cognition and memory postoperatively. Interpretation: As an extra‐axial tumor, PitNET may exhibit distinctive cognitive and affective functioning compared to intra‐axial tumors, highlighting the need for specific treatment approaches for PitNET patients. [ABSTRACT FROM AUTHOR]