Abstract: When the International Agency for Research on Cancer (IARC) classified shift-work that involves circadian disruption as probably carcinogenic to humans in 2007, this was the prelude to extensive experimental and epidemiological research in coming years. Indeed, with some 20% of people worldwide being engaged in some type of work at unusual times, including the night, it is a must to investigate, and to clarify as soon as possible, the biologically plausible links via circadian disruption with epidemic cancers such as of the breast or prostate. Surprisingly, neither the IARC information available so far nor the general literature provides a clear definition of what the critical component in the postulated chain of causation, namely circadian disruption, is. Here we offer our definition of chronodisruption (CD), a concept which we proposed in 2003 and which we operationalized recently in research which addressed the putative links between shift-work, time-zone-travel and human cancers independently of the IARC and led to similar causal interpretations. As a basis for further research in this area with possible high relevance for public health, we: (i) elaborate our definition of CD, with melatonin being a key biological intermediary, by putting critical disruptions, and the resulting disorder, of circadian clocks, biological rhythms and circadian organization into thematic and historical context with Colin Pittendrigh’s insights almost half a century ago; (ii) provide material on ‘what are chronodisruptors?’ and (iii) pose a key question which needs to be answered by and for experimental and epidemiological CD research. We hope that defining CD can contribute to studies which may help to find clues to a background incidence of epidemic internal cancers for which – so far in many cases – we lack causal explanations.