The human tumor phenotype referred to as MSI (Microsatellite Instability) is associated with inactivating alterations in MMR genes (Mismatch Repair). MSI was first observed in inherited malignancies associated with Lynch syndrome and later in sporadic colon, gastric and endometrial cancers. MSI tumors develop through a distinctive molecular pathway characterized by genetic instability in numerous microsatellite DNA repeat sequences throughout the genome. In this article, french researchers and physicians who have been recently awarded by the Fondation de France (Jean and Madeleine Schaeverbeke prize) make a sum of their activity in the MSI cancer field for more than 20 years. Their findings have greatly contributed to increase our knowledge of this original cancer model, laying the foundation for a personalized medicine of MSI tumors.