Ethyl tert-butyl ether (ETBE), a fuel additive, and tert-butyl alcohol (TBA), a solvent and metabolite of ETBE and methyl tert-butyl ether (MTBE), may be encountered via inhalation, oral, or dermal exposure. This assessment evaluated the human carcinogenic hazard of ETBE and TBA by systematically reviewing available human, animal, and mechanistic data. No epidemiological studies were identified, and two standard cancer bioassays were available for each compound. Tumor responses were limited to low incidences at high exposure levels: liver tumors in male F344 rats, kidney tumors in male F344 rats, and thyroid tumors in female B6C3F1 mice exposed to ETBE or TBA, respectively. Mechanistic evidence was organized within the framework of the key characteristics of carcinogens (KCC) and established rodent non-genotoxic modes of action (MoAs) for the overall evaluation. Aside from supportive evidence for KCC2 (is genotoxic) and KCC10 (alters cell proliferation, death, or nutrient supply), mechanistic data across KCCs were sparse and inconsistent. Both substances lacked genotoxic activity with available data supporting non-genotoxic MoAs that are not relevant to humans. Overall, the evidence indicates little concern for a carcinogenic hazard of ETBE or TBA in humans.