Background: Radiologically isolated syndrome (RIS) is typified by multiple sclerosis (MS)-like lesions on imaging, without clinical MS symptoms. The prevalence of pediatric RIS is largely unknown. Objective: The objective of the study is to provide an estimated RIS prevalence in a population-based cohort of children. Methods: We used data from the Generation R study to identify the childhood RIS prevalence. Results: In 5238 participants, only one RIS case was identified (prevalence: 0.02%; 95% confidence interval (CI): 0.00–0.11). During a 62-month follow-up, imaging examinations showed accrual of new focal demyelinating lesions; however, no clinical MS symptoms occurred. Conclusions: This study shows that the occurrence of RIS in children from the general population is rare.