Following reports of ten cases of ALS that occurred in a village in Savoie with approximately 900 residents between 1991 and 2013, and ten cases that occurred between 2000 and 2013 in a municipality in Isère with approximately 6,500 residents, an investigation was conducted to determine whether there was an excess of ALS cases, identify a possible common exposure, and assess the role of chance in the event of an excess. The methodological approach included a descriptive study of the cases, the estimation of standardized mortality ratios (SMR) for ALS, an analysis of their geographic distribution by municipality, the estimation of an “adjusted” SMR (using an empirical Bayesian estimator), and the identification of potential sources of environmental exposure. The SMRs are approximately 10 and 2, respectively, in the municipalities of Savoie and Isère. The analysis of the "adjusted" SMRs suggests that the heterogeneous geographic distribution of ALS deaths is linked to the random distribution of the disease. Cases residing in these municipalities do not differ, in terms of age and sex, from the sporadic cases described in the literature. No spatial clustering within the municipalities, no factor suggesting a shared exposure, nor any specific exposure capable of explaining all or part of the observed cases could be identified. These results do not support the hypothesis of a link between the observed ALS cases and a specific risk currently present in these municipalities. As with other diseases whose risk factors are unknown, there are no specific management measures that, if implemented, could prevent the onset of this disease. Surveillance has been maintained, and the situation would have been reassessed if new cases had emerged. Since then, no new cases have been reported. Baseline data will soon be available for the entire territory. These data could also be used to explore hypotheses regarding environmental exposures in the occurrence of this still poorly understood disease.