The replication of the undamaged genomic DNA requires error-free DNA polymerases delta and epsilon as part of a protein complex that acts continuously along the double helix. In contrast, when the genomic structure is perturbed, DNA replication needs to function more flexibly to bypass DNA distortions. It has been proposed that the newly discovered error prone DNA polymerases play a role in the replication of irregular structure. Here we report that one of them, the human Polkappa, is mostly localised uniformly in the nucleus of undamaged cells, but could be also concentrated in PCNA-containing replication foci. Following treatment with anti-replicative agents, the proportion of foci-containing cells was increased. These data suggest that Polkappa may function as part of the replication machinery itself and could be recruited when replicative complexes are stalled. Mutagenesis experiments also indicated that Polkappa involvement may affect the accuracy of DNA replication. The results are discussed within the context of the oncogenic process since Polkappa has been found as overexpressed in some cancers.