There is now an increasing recognition of the need to develop robust preclinical safety biomarkers, as elucidated in various reports (FDA (2006), NRC(2007)). A primary focus is to develop prediction rules for different types of toxicities, especially non-genotoxic carcinogenicity, since this occurs in a significant proportion of compounds tested in rodents, and for which short-term assays have been difficult to develop. In this talk, we describe a novel approach for developing genomic prediction rules for non-genotoxic carcinogenicity based on 24-hr microarray studies on rats. Our methodology offers a robust and clearly generalizable approach for developing such rules in a variety of other settings. We also briefly describe an independent effort currently underway at the PSTC to develop and validate a custom genomic assay based on genes culled from published literature.