At the beginning of this century Theodor Boveri predicted that specific chromosome changes would be found to have a causal role in neoplasia. We are now beginning to acquire the evidence to substantiate this hypothesis. The evidence comes from two particular sources, (i) genetic environmental interactions and (ii) specific constitutional chromosome aberrations. Cancer incidence varies throughout the world. This is often due to the interaction of an environmental agent with a genetically varied population. Using UV and ionising radiation as examples it is argued that some individuals are more susceptible to genetic damage by these agents. Moreover, the genetic lesions which are caused by these agents are now being shown to be relevant to cancer. In the radiosensitive syndrome ataxia-telangiectasia for example, specific chromosome rearrangements have been defined which seem likely to be directly involved in the development of leukaemia in these patients. The second line of evidence comes from the study of patients who have constitutional chromosome abnormalities associated with susceptibility to specific cancers. It has now been shown that these chromosome changes mark the location of genes which are involved in the development of cancer and that these same loci are also important in the non-familial forms of these diseases. Thus we are beginning to understand for the first time the mechanistic pathway that leads from environmental agents, through chromosome damage, to the alteration of specific genes which control the neoplastic process.