In September 2019, the Pays de la Loire Regional Health Agency referred a case to Santé publique France to investigate a suspected cluster of cancers among children under the age of 18, consisting mainly of malignant hematological diseases and reported in a rural area in the eastern part of the Pays de la Loire region. The investigation was conducted in accordance with the national guidelines for the assessment and management of spatio-temporal clusters of non-infectious diseases. To validate the spatio-temporal cluster, the method employed involved a retrospective search to determine whether an excess of cases of malignant hematological diseases was observed in a defined geographic area, compared to cancer rates observed in mainland France. The investigation was conducted among 5 children under the age of 18 at the time of diagnosis, established between 2016 and 2020, and residing in a contiguous geographic area comprising 6 municipalities. It confirmed the presence of an excess incidence of malignant hematological diseases in the study area for the period in question. An environmental assessment was conducted on known environmental risk factors for malignant hematological diseases using several existing databases. This study did not aim to identify individual causes for each cancer but rather to identify a common factor among the affected children that is specific to the geographic area. The investigation did not identify any environmental factor common to the majority of affected children that could serve as an explanatory hypothesis for this cluster. Thus, the hypothesis of a random clustering of affected children appears to be the most likely explanation. In light of these findings, and in accordance with the guidelines for investigating spatio-temporal clusters, Santé publique France does not recommend continuing the epidemiological investigation with an etiological study, nor conducting additional environmental analyses.