Drinking water must be disinfected prior to its distribution for human consumption. This water treatment process generates disinfection by-products (DBPs), formed by the interaction of the disinfectant with organic matter, anthropogenic contaminants and inorganic (bromide/iodide) matter naturally present in source water. Due to the potential genotoxic/carcinogenic risk of these DBPs, we have investigated the mutagenic potential of six of such compounds on the thymidine kinase ( Tk) gene in the well-validated mouse lymphoma assay (MLA). The MLA quantifies a wide range of genetic alterations affecting the expression of this gene in L5178Y/ Tk +/−-3.7.2C cells. In this study we selected six emerging DBPs, corresponding to three different chemical classes: halonitromethanes (bromonitromethane and trichloronitromethane), halogenated acetaldehydes (tribromoacetaldehyde and chloral hydrate) and hydroxyfuranones (mucobromic and mucochloric acids), each class including one chlorinated and one brominated form. The results showed that after 4 h of treatment, only mucobromic acid increased the frequency of mutant colonies, with a higher proportion of small colonies, which would indicate a clastogenic potential. This is the first study reporting mutagenicity data in mammalian cells for the six selected DBPs.