CHFR (Checkpoint with Forkhead-associated and RING finger domains) has been implicated in a checkpoint regulating entry into mitosis. However, the details underlying its roles and regulation are unclear due to conflicting lines of evidence supporting different notions of its functions. We provide here an overview of how CHFR is thought to contribute towards regulating mitotic entry and present possible explanations for contradictory observations published on the functions and regulation of CHFR. Furthermore, we survey key data showing correlations between promoter hypermethylation or down-regulation of CHFR and cancers, with a view on the likely reasons why different extents of correlations have been reported. Lastly, we explore the possibilities of exploiting CHFR promoter hypermethylation status in diagnostics and therapeutics for cancer patients. With keen interest currently focused on the association between hypermethylation of CHFR and cancers, details of how CHFR functions require further study to reveal how its absence might possibly contribute to tumorigenesis.