Diffuse leptomeningeal glioneuronal tumor has various clinical manifestations and is easily misdiagnosed. This article aims to describe the clinical features of a patient with diffuse leptomeningeal glioneuronal tumor misdiagnosed as optic neuromyelitis lineage disease (NMOSD), analyze the causes of misdiagnosis, and identify the disease with similar clinical manifestations. Adolescent women with decreased vision and headache, nausea, and vomiting were initially diagnosed as NMOSD. Immunotherapy was ineffective; enhanced MRI and cerebrospinal fluid cytology examination were completed and compared with classic meningeal carcinoma, NMOSD, multiple sclerosis, and Vogt-Koyanagi-Harada (VKH) syndrome. Diffuse leptomeningeal glioneuronal tumor was finally diagnosed in adolescent women with no history of tumor. Compared with NMOSD: no history of infection, no AQP4, MOG antibody, no spinal segmental abnormalities, immunotherapy was ineffective; compared with multiple sclerosis: no history of infection, no plaque, no oligoclonal antibody, immunotherapy was ineffective; compared with VKH syndrome: no history of infection, no fever, no treatment for immunotherapy; and compared with classic meningeal carcinoma: adolescents, no extracranial tumor lesions, super high protein, more different sugar excess. Patients with acute visual impairment should consider not only NMOSD, but also diffuse leptomeningeal glioneuronal tumor (DLGNT) and other diseases. DLGNT could not be excluded when CSF cytology and MRI plain scan were negative. The positive rate of malignant cells can only be increased by repeatedly sending fresh cerebrospinal fluid for examination; DLGNT needs to be differentiated from NMOSD, multiple sclerosis, VKH syndrome, and other diseases. Early diagnosis and molecular targeted therapy can improve the quality of life and prolong life.