DNA mutation events (gene rearrangements, base-pair substitutions) cause genomic instability, and can lead to cell death or cancer. These events also potentially lead to gene dysfunction and genetic disorders. DNA mutation events have many possible causes, such as inherited mutations in genes involved in genomic integrity, or exposure to environmental toxins. Human stem cell technology, in which stem cells can be differentiated into any cell type in the body, has the great potential to advance the discovery of therapeutics for unmet medical needs. However, recent reports indicate increased DNA mutation frequency in stem cells, which limits their potential use for discovery or therapeutic purposes. Therefore, technologies that enable the detection of the different types of DNA mutations would advance the characterization and selection of human stem cell lines for discovery or therapeutic purposes, and help characterize the mutagenic potential of environmental toxins.