The past several decades have seen a paradigm shift with the integration of evolutionary thinking into studying cancer. The evolutionary lens is most commonly employed in understanding cancer emergence, tumour growth and metastasis, but there is an increasing realization that cancer defences both between tissues within the individual and between species have been influenced by natural selection. This special issue focuses on discoveries of these deeper evolutionary phenomena in the emerging area of ‘comparative oncology’. Comparing cancer dynamics in different tissues or species can lead to insights into how biology and ecology have led to differences in carcinogenesis, and the diversity, incidence and lethality of cancers. In this introduction to the special issue, we review the history of the field and outline how the contributions use empirical, comparative and theoretical approaches to address the processes and patterns associated with ‘Peto's paradox’, the lack of a statistical relationship of cancer incidence with body size and longevity. This burgeoning area of research can help us understand that cancer is not only a disease but is also a driving force in biological systems and species life histories. Comparative oncology will be key to understanding globally important health issues, including cancer epidemiology, prevention and improved therapies.