Background: Cranial radiation is known to increase the relative risk for developing a second primary neoplasm, but existing analyses do not take into account differential survival or follow-up. The absolute risk, or true incidence, of developing a second primary neoplasm in the central nervous system (CNS) is not well characterized. Methods: Patients diagnosed with cancer from between 1976 and 2016 were sampled using the Surveillance, Epidemiology, and End Results (SEER) Program. Relative risks were estimated using standardized incidence ratios (SIRs) and absolute risks were estimated using cumulative incidence (CI) functions with death as a competing risk. Among CNS primaries, comparison groups were matched by age, sex, year of diagnosis, primary histology, and lesion location. Results: Over 3.8 million patient records, including 13,167 second primary CNS tumors, were extracted from SEER. The relative risk of developing a second primary CNS neoplasm is elevated in all patients diagnosed with a CNS primary cancer (SIR = 9.6), but higher in those who received radiation (SIR = 13.1) or chemotherapy (SIR = 12.6). The absolute risk of developing a second primary CNS neoplasm at 25-years is highest in CNS and endocrine cancers (CI 1.0% and 0.50%, respectively). Among long-term ( > 10-year) survivors of CNS primaries, the 25-year CI of a second primary CNS neoplasm was 4.4%. Cranial radiation increased the incidence of second primary tumors in pediatric patients (25-year CI 4.8% vs 1.2%, p = 0.007), but not adults (25-year CI 5.1% vs 4.9%, p = 0.85). Chemotherapy did not increase CI in either pediatric (25-year CI 7.0% vs 5.4%, p = 0.87) or adult (25-year CI 3.6% vs 5.8%, p = 0.11) populations. Meningiomas (39.3% vs 22.0%, p = 1e-6) and glioblastomas (21.1% vs 14.6%, p = 0.03) represent a greater proportion of the second primary CNS tumors in those who received cranial irradiation. Conclusions: The risk of developing a second primary CNS neoplasm is elevated in patients with a prior CNS cancer. Cranial irradiation increased the CI of second primary tumors in pediatric patients but did not affect adult patients. The association between radiation therapy and risk for subsequent cancers may be limited to the pediatric population.