Deciphering the relative contribution of intrinsic (e.g., genetic) and extrinsic (e.g., life style, environmental) risk factors in cancer development is crucial for strategizing cancer prevention. The recent publication by Wu and colleagues in Nature appears as an important contribution to the debate previously initiated by Tomasetti and Vogelstein in Science, who proposed that two-thirds of cancers can be attributed to random mutations and hence 'bad luck'. By contrast, Wu and colleagues, using four lines of evidence, suggest that cancer risk is dominated by extrinsic factors, and intrinsic risk factors only contribute marginally. The debate remains open, and an approach focusing on the evolutionary ecology of organs could provide crucial insights.