Recently discovered targeted therapies for melanoma have proved good response in patients. However such treatments are limited by rapid development of drug resistance, instigating research towards the identification of novel therapeutic targets. Cell cycle checkpoints are control mechanisms that preserve genomic integrity and control cell proliferation. Defective cell cycle checkpoints provide obvious growth advantages to tumours, however they are also thought to increase cell reliance on survival mechanisms in order to cope with accumulation of DNA damage. We have observed that almost 70% of melanoma cell-lines have a defective G2-phase decatenation checkpoint. Indeed, these cells don’t arrest cycling, or do so only partially, under persistence of catenated chromosomes, a condition known to trigger decatenation checkpoint activation. We show that despite the lack of cell cycle arrest, checkpoint signalling through ATM/Chk2 activation is intact. Moreover, preliminary data suggest that improper regulation of Plk1 and Bora proteins during checkpoint activation might be responsible for the lack of cell cycle arrest. The dysfunction of the decatenation checkpoint commonly observed in melanoma might be exploited as a chemosensitizer or as a source of cellular compensatory mechanisms that can be targeted for selective therapy. Elucidation of the molecular mechanisms of this dysfunction might therefore prove beneficial for amelioration of melanoma treatment.