Extract: Despite tremendous efforts to understand mechanisms of cancer initiation and development, many mysteries of this terrible disease are still unresolved. Why does cancer incidence rate, after a steady increase during adulthood, decelerate or even decline at the oldest ages? It seems counter-intuitive because aging is believed to be associated with increased risks of chronic pathology. Why has overall cancer risk increased along with economic progress, while medical and living conditions have greatly improved in the developed world? Answering these questions is of key importance for developing successful cancer prophylaxis. The latter showed rather few breakthroughes during past decades despite the amount of efforts spent on developing strategies of cancer prevention. Numerous studies have been focused on clinical and genetic aspects of cancer in laboratory animals to help understanding cancer in humans, as well as the role of environmental carcinogenic factors in cancer risk. However, epidemiological aspects of cancer manifestation in different mammalian species have been rather under-represented in the literature. Recent review by Anisimov, Ukraintseva, and Yashin (2005) draws readers' attention to comparative cancer epidemiology in mice and men, claiming this knowledge to be critical for developing successful prophylaxes of human cancers. The focus of the paper is on two most intriguing hallmarks of cancer epidemiology: (i) deceleration or decline in human cancer risk in the oldest age; and (ii) increasing the overall cancer risk in human history. Although some studies suggested plausible explanations of these phenomena, exact reasons for the surprising behavior of cancer incidence rates are not clear so far.