Introduction Histiocytic sarcoma (HS) rarely affects the central nervous system (CNS) and often presents with nonspecific neurological symptoms, making diagnosis challenging. We report, to our knowledge, the first case of CNS-HS with concurrent skull base infiltration and intraventricular dissemination, highlighting the diagnostic challenges of this aggressive disease. Methods An 18-year-old woman with a 9-month history of progressive headaches and seizures was initially misdiagnosed with viral meningitis. She subsequently underwent brain magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and neuroendoscopic biopsy via a lateral ventricle approach to establish a definitive diagnosis. Results MRI revealed a lesion in the right medial temporal lobe with extensive skull base infiltration and intraventricular dissemination. CSF analysis demonstrated hypoglycorrhachia (low CSF glucose) and elevated protein levels without pleocytosis. Histopathology confirmed HS, with tumor cells strongly positive for CD68 and CD163. Discussion This case illustrates the diagnostic challenges of CNS-HS and underscores the importance of advanced neuroimaging, metabolic CSF analysis, and early biopsy in patients with atypical neurological presentations. Given the rapid progression and poor prognosis, early recognition and comprehensive molecular profiling may facilitate targeted therapies.