Cancers can be considered as gene diseases. A number of mechanisms leading to cancer have been identified through the discovery of structural alterations of genes called 'oncogenes' and 'tumour suppressor genes'. Somatic and germinal mutations are rare but play a determinant role in the emergence of cancer, while common and frequent variations (polymorphisms) play a role in cancer susceptibility and in the effects of anticancer drugs (efficacy and toxicity). After a general overview on the structural and functional organisation of the human genome, we present here some of the techniques aimed at the identification of structural DNA variations. We present afterwards some examples of the role that play polymorphic constitutive variations of the genome in the occurrence of cancer (molecular epidemiology) and the activity of anticancer drugs (pharmacogenetics).