In March 2017, the town hall of a municipality in Isère with 1,600 residents reported a suspected cluster of glioblastomas among its residents to the Auvergne-Rhône-Alpes Regional Health Agency (ARS ARA). Investigations were conducted by the regional office of Santé publique France in accordance with the recommendations of the methodological guide for the assessment and management of spatio-temporal clusters of non-infectious diseases published in 2005 by the Institute for Public Health Surveillance (InVS), now Santé publique France. Case validation and incidence calculations were facilitated by the existence of a general cancer registry for the department of Isère. This registry provided the number of cases of glioblastomas and other central nervous system tumors recorded in the municipality and throughout the department of Isère from 2002 to 2016. For the most recent cases, information was also provided by the neurosurgery department that treated them. Ultimately, seven cases of glioblastoma occurred between 2002 and 2016 among residents of this municipality in Isère, which is nearly seven times the “expected” number. The probability of observing such an excess of glioblastoma cases is low, but not zero, given the random distribution of diseases in a small population. In the municipality, the research conducted did not identify any environmental risk factors among those mentioned in the scientific literature that could explain this excess of cases. Based on this investigation and in the absence of new information regarding collective or individual exposures of the cases to glioblastoma risk factors, it cannot be ruled out that this cluster of cases is linked to the random distribution of this disease in a small population. However, given the number of glioblastoma cases observed, it is recommended that particular vigilance be maintained in this municipality in order to identify the occurrence of additional cases, the reporting of which would confirm the unusual nature of this cluster.