This manuscript addresses how epidemiology might benefit from the sequencing of the human genome in terms of identifying the aetiology of cancer. Given that most human cancer is the result of both genetic and environmental risk factors, accurate assessment of both is required to develop an understanding of molecular mechanisms of carcinogenesis. Sequencing the human genome is a major scientific advance, which needs to be considered in the context of the multifactorial aetiology of cancer if it is to bring the maximum benefit. Likewise, assessment of environmental exposure is challenging for a number of reasons, particularly when exposures are relatively low level and vary over time. Biomarkers of environmental exposures (e.g. carcinogen-DNA and -protein adducts) offer the potential to overcome some of these limitations. Furthermore, markers of genetic alterations may permit the detection of relevant early stages of malignancy to inform surveillance and effective treatment, and provide an approach to disease classification. We conclude that in order to progress our understanding of cancer aetiology, a balanced approach integrating molecular measures into well-designed epidemiological studies is required.