We report the case of a 1-year-old male patient with systemic juvenile xanthogranuloma in whom central nervous system lesions caused developmental retardation, spasticity and clonus of the lower extremities. He needed tube feeding and experienced severe bronchitis and generalised convulsive seizure. KIF5B-ALK fusion was identified in the cutaneous lesion, and he was administered alectinib, an ALK inhibitor. Two months after the initiation of alectinib administration, the central nervous system lesions achieved partial regression. The spasticity and clonus were also relieved. A high index of cognition is needed for ALK fusion in infants with histiocytosis.