In October 2019, the Normandy Regional Health Agency asked Santé publique France to investigate a suspected cluster of pediatric cancers in the Eure department, as reported by parents of affected children. To assess the spatial and temporal clustering, the method used involved a retrospective analysis to determine whether an excess of pediatric cancers was observed in a defined geographic area, compared to cancer rates observed in mainland France. Cancers identified between 2017 and 2019 were included. Two analyses were conducted: one for all cancers and the other for leukemias, the most common cancer in children. Two geographic areas were defined: one at the municipal level, maximizing the risk of observing an excess incidence, and the other at the cantonal level, minimizing the risk of observing an excess incidence. The investigation identified 11 children diagnosed with cancer during the study period. No excess of cases was found when all cancers were considered. When the analysis was restricted to cases of leukemia, an excess of cases was found in the geographic area corresponding to a group of municipalities (SIR = 6.4 [2.3–14.0]). This excess was not observed when the analysis focused on the cantonal grouping (SIR = 2.3 [0.8–5.0]). An epidemiological study was conducted using a questionnaire administered to parents, and an environmental assessment was performed on known environmental risk factors. This study did not aim to identify individual causes for each cancer but rather to identify a common factor among the children, specific to the geographic area, that could explain the cluster of cases and on which action could be taken. The investigations did not identify any common factor among the affected children, and the environmental assessment did not reveal any specific features. In the absence of an etiological hypothesis, conducting a specific environmental monitoring campaign was not warranted. Consequently, in the absence of identified environmental and epidemiological causes, the hypothesis retained based on the current state of knowledge is a one-time cluster of pediatric cancer cases. Santé publique France recommends continuing to monitor the occurrence of new cases of pediatric leukemia in the geographic area.