The pH 6.7 Syrian hamster embryo (SHE) cell morphological transformation assay is a short-term in vitro test that has been used to predict rodent carcinogenicity. Previous reports have indicated that the SHE assay has an overall concordance of approximately 80% with the 2 year rodent bioassay. We selected five compounds, genistein, metaproterenol, rotenone, p-anisidine and resorcinol, that had extensive genotoxicity and carcinogenicity data and tested them in the standard 7 day exposure SHE assay. Somewhat surprisingly, the SHE assay misclassified the actual rodent carcinogenicity of four out of the five test compounds. It is difficult to explain these findings as the actual mechanisms of SHE cell morphological transformation are currently unknown. However, it is obvious that in these studies there was no simple correlation between in vitro genotoxicity, morphological transformation in SHE cells and rodent carcinogenicity. Clearly, further research is required to accurately assess the role of the SHE assay in the carcinogenic risk assessment of new chemical entities.