It is important to establish sensitive and reliable method for genotoxicity tests for evaluating the potential mutagenicity of chemicals. In recent years, a new in vivo genotoxicity test based on Pig?a gene mutation has been developed and recognized to be useful for regulatory safety assessment because of its potential for clinical translation, its remarkable sensitivity to mutagenic agents, its relatively low cost, and its potential for integration with other in vivo tests as well as for reducing animal use. This paper mainly reviews the application and development of the Pig?a gene mutation assay.