Juvenile myelomonocytic leukemia is a rare malignancy that occurs in pediatric patients. Previous reports, have described leukemic cells may infiltrate many organs, such as the lungs, skin, liver, spleen, and intestines, but not the central nervous system, although central nervous system infiltration remains a point of concern in every patient with acute leukemia. Here, we present one case of a boy with juvenile myelomonocytic leukemia who developed multiple lesions in the brain while undergoing chemotherapy with 6-mercaptopurine and cytarabine. We diagnosed the central nervous system involvement by magnetic resonance imaging, cerebrospinal fluid cytology, and the patient's clinical course. He was treated with a high dose of cytarabine and intrathecal chemotherapy, then with unrelated cord blood stem cell transplantation. He has been in a first complete remission for more than 18 months after cord blood stem cell transplantation without any neurological sequelae. In conclusion, we encountered a boy with juvenile myelomonocytic leukemia who developed central nervous system lesions under standard chemotherapy. We subsequently switched treatment to central nervous system-oriented chemotherapy, which resulted in a good clinical condition and successful cord blood stem cell transplantation.