CIP2A is an inhibitor of the tumour suppressor protein phosphatase 2A. Recently, CIP2A was identified as a synthetic lethal interactor of BRCA1 and BRCA2 and a driver of basal-like breast cancers. In addition, a joint role of TopBP1 (topoisomerase IIβ-binding protein 1) and CIP2A for maintaining genome integrity during mitosis was discovered. TopBP1 has multiple functions as it is a scaffold for proteins involved in DNA replication, transcriptional regulation, cell cycle regulation and DNA repair. Here, we briefly review details of the CIP2A–TopBP1 interaction, its role in maintaining genome integrity, its involvement in cancer and its potential as a therapeutic target.