Background: Disseminated juvenile xanthogranuloma (JXG) and central nervous system (CNS) involvement has unfavorable outcome. Observation: A 3.5-year-old presented with headache, left hemiparesis of 2 weeks duration and encephalopathy, polyuria, polydipsia of > 6 months, multiple skin lesions from infancy, diagnosed as JXG with diabetes insipidus. Regression for >2 years was observed with Langerhans Cell Histiocytosis (LCH)-III protocol, desmopressin. Relapse after six months off-treatment was treated with LCH-IV protocol, later with salvage regimen; maintenance therapy for a year and now in remission for > 6 years. Conclusions Good neurological outcome is possible in chemo sensitive JXG is despite extensive CNS lesions.