Contemporary oncological research is predominantly characterised by genetic explanations, a situation which may be briefly denoted as the oncogene paradigm. This essay discusses why the new paradigm was perceived so attractive that it could take over the whole field of oncology within a time-span of less than two decades. It is argued that the revolutionary character of the oncogene paradigm stems from the fact that it transcends a dichotomy which has kept experimental cancer research divided for more than three quarters of a century. This concerns the dichotomy between so-called exogenous and endogenous explanations of cancer causation. This essay mainly focuses on the role of the exogenous/endogenous dichotomy in the reception of research on oncogenic viruses, especially discussing the work of Nobel laureate Peyton Rous on cancer viruses at the Rockefeller Institute. Rous was severely criticised by James Ewing, director of the Memorial Hospital for Cancer and Allied Diseases in New York, who held the idea that the origin of cancer was based in the cell. The twentieth century controversy over oncogenic viruses is placed in the context of the intense discussion over causality in medicine during the first decades of the twentieth century in Germany. It is argued that the oncogene paradigm may be seen as revolutionary because it succeeded in uniting the exogenous and endogenous explanations of cancer in a single paradigm.