Brainstem glioma is a highly devastating disease, and any mass-like lesion in the brainstem can raise suspicion of this diagnosis. However, other inflammatory, demyelinating, or degenerative diseases can mimic brainstem glioma in clinical presentation and imaging features. Therefore, diagnosis based solely on imaging is often insufficient for brainstem lesions and may lead to incorrect diagnosis and treatment. This case report is the first description of central nervous system aquaporin-4 (AQP4) autoimmunity confined mainly to the brainstem. It demonstrates the wide spectrum of neuroinflammatory diseases in children and highlights the utility of surgical biopsy for suspicious brainstem lesions with atypical imaging features for glioma.