We investigated retrospectively 992 children with central nervous system tumors who were treated at our center between 1970 and 2004. All of the patients were treated by surgery, chemotherapy, and/or radiotherapy. Six patients developed second malignant neoplasms, and their clinical and histopathologic characteristics are reviewed in this article. The second malignant neoplasms were diagnosed as non-Hodgkin lymphoma, myelodysplastic syndrome, basal cell carcinoma, malignant melanoma, Kaposi sarcoma, and high-grade neuroectodermal tumor. The initial diagnoses were ependymoblastoma in one, medulloblastoma in three, and low-grade astrocytoma in two patients. The median latency time was 3.03 years (range 0.39-22.93 years). The outcome varied according to the histopathologic type of the second tumor. The patients who developed non-Hodgkin lymphoma, and myelodysplastic syndrome died of progressive disease. The patients with second skin neoplasms are alive as of the time of this writing. The patient with Kaposi sarcoma developed one of the rare reported second malignant neoplasms following a primary brain tumor in childhood. A wide spectrum of second malignant neoplasms was detected after treatment of primary brain tumors with surgery, radiotherapy, and chemotherapy. Long-term follow-up is therefore necessary for the child who has survived a primary central nervous system tumor.