Genetic instability contributes to the development and progression of gastric cancer, one of the leadingcauses of cancer death worldwide. Microsatellite instability (MSI) has been hypothesized to be involved incarcinogenesis, althgough its mechanisms and exact roles in gastric cancer remain largely unknown. Our aimwas to identify associated clinicopathological characteristics and prognostic value of MSI in gastric cancer andprecancerous lesions including gastritis, metaplasia, dysplasia, and adenoma. Because mitochondrial DNA hasa different genetic system from nuclear DNA, the results of both nuclear MSI and mitochondrial MSI in gastriccancer were reviewed. This review provides evidence that genetic instability of nuclear and mitochondrial DNAscontributes to early stages of gastric carcinogenesis and suggests possible roles in predicting prognosis.