Juvenile xanthogranulomatosis (JXG) is an uncommon histiocytic disease that is usually limited to the skin. Here we describe an infant with systemic JXG including a central nervous system (CNS) lesion. He was initially treated with prednisolone and vinblastine but developed an idiosyncratic reaction to prednisolone that was discontinued. The lesion then failed to respond to vinblastine monotherapy. Treatment with cladribine (2-chlorodeoxyadenosine) was subsequently successful with radiological resolution of the CNS lesion.