: For two decades, research has been suggested and conducted into the causation and development of cancers in seemingly diverse and unrelated populations such as blind individuals, shift-workers, flight personnel, Arctic residents and subsets of sleepers. One common denominator of these investigations is "melatonin". Another common denominator is that all these studies implicitly pursued the validity of the so-called "melatonin hypothesis", of a corollary and of associated predictions which can be united in our proposed theory of "carcinogenesis due to chronodisruption". The new theory suggests that the various predictions investigated between 1987 and 2008 represent different aspects of the same problem. Indeed, abundant experimental evidence supports the notion that the final common cause of many cases of cancer may be what has been termed chronodisruption (CD), a relevant disturbance of the temporal organization or order of physiology, endocrinology, metabolism and behaviour. While melatonin as a key time messenger and time keeper can be a marker of CD, it is probably only partially related to the differential cancer occurrence apparent in individuals who chronically or frequently experience an excess or deficit of chronodisruption.