Microsatellite instabilities (MIN) represent a new type of mutation characterized by genomic instability (or replication error phenotype, RER+). First identified in sporadic and familial colorectal tumors, the RER+ phenotype has been sought in multiple types of cancers. Thus, two types of instability mechanisms have been shown: one due to inactivation of the mismatch repair system (phenotype RER+) and a second still unclear (instability of tri- and tetra-nucleotide repeats). In both cases, MIN seem to be the reflect of a new tumorigenesis pathway. In the context of mismatch repair defect, numerous observations show that, although instabilities seem to be random, they play a direct role in the tumoral process by altering genes that control cell growth and apoptosis. Today, MIN, as well as the detection of mutations in the DNA mismatch repair genes, can be used as diagnosis tools in oncology and provide usefull indications to adapt the chemotherapy to the disease.