Pold2 is a subunit of the DNA polymerase δ complex, encoding a protein involved in DNA replication and repair. In this study, using a yeast two-hybrid screening technique and the common cDNA fragment of the mouse PIAS2 as a bait, Pold2 was found to interact with PIAS2. A direct interaction between Pold2 and PIAS2 was confirmed by direct yeast two-hybrid. In vivo evidence of Pold2 association with PIAS2 was obtained by co-immunoprecipitation using HEK-293 cells. Subcellular localization studies demonstrated that Pold2 and PIAS2 were partially co-localized in mammalian cells. Collectively, our results suggest that Pold2 interacts under physiological conditions with PIAS2.