The paper provides the first assessment of the occurrence of hormetic dose responses using the Comet assay, a genotoxic assay. Using a priori evaluative criteria based on the Hormetic Database on peer-reviewed comet assay experimental findings, numerous examples of hormetic dose responses were obtained. These responses occurred in a large and diverse range of cell types and for agents from a broad range of chemical classes. Limited attempts were made to estimate the frequency of hormesis within comet assay experimental studies using a priori entry and evaluative criteria, with results suggesting a frequency in the 40% range. These findings are important as they show that a wide range of genotoxic chemicals display evidence that is strongly suggestive of hormetic dose responses. These findings have significant implications for study design issues, including the number of doses selected, dose range and spacing. Likewise, the widespread occurrence of hormetic dose responses in this genotoxic assay has important risk assessment implications.