Cdk10 is a Cdc2-related kinase that may play a role in regulating the G2/M phase of the cell cycle. However little is known about the proteins that interact with this putative kinase and contribute to its function in the cell. We report in this study that Cdk10 interacts with the N-terminus of the Ets2 transcription factor, which contains the highly conserved Pointed domain and transactivation domain. The Pointed domain has been implicated in protein-protein interactions and we find that Ets2 requires an intact Pointed domain to bind Cdk10. The Pointed domain of Ets1 is highly similar to Ets2, however Cdk10 does not recognize Ets1 in a two-hybrid assay thereby demonstrating significant binding specificity on the part of Cdk10. We find that Cdk10 binds full length Ets2 in vitro and in vivo and inhibits Ets2 transactivation in mammalian cells.