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Diffuse astrocytoma (DA) is the most common intraparenchymal brain tumor, primarily occurring in the frontal and temporal lobes. However, its occurrence in the lateral ventricles is rare. We report a rare case of a 57-year-old male with DA in the lateral ventricle. The patient presented with a one-day history of headache, nausea, and vomiting. Computed tomography (CT) revealed a round, low-density lesion in the right lateral ventricle. Magnetic resonance imaging (MRI) showed a T2-weighted/fluid-attenuated inversion recovery (T2/FLAIR) mismatch, low signal on diffusion-weighted imaging (DWI), reduced perfusion on arterial spin labeling (ASL), and no enhancement after gadolinium administration. Postoperatively, the patient's condition was initially stable but deteriorated rapidly on the third postoperative day, ultimately resulting in death several months later. Pathological evaluation revealed extensive microcyst formation, homogeneous tumor cell nuclei, and a tumor composed predominantly of moderately dense fibrous-type neoplastic cells within a microcystic matrix, with no mitosis, necrosis, or microvascular proliferation. Immunohistochemical analysis showed positive expression for GFAP, Olig-2, and IDH-1, with a Ki67 proliferation index of approximately 4%. The pathological diagnosis was diffuse astrocytoma (NOS). This report details a rare case of headache caused by lateral ventricular diffuse astrocytoma characterized by typical T2/fluid-attenuated inversion recovery (FLAIR) mismatch signs. Despite the benign nature of lateral ventricle DA, surgical intervention necessitates manipulation of critical neural structures, including the corpus callosum and cortex, attributed to the tumor’s deep-seated location. Reducing postoperative complications and mortality remains a significant challenge.