The increasing incidence of RCC in most populations may in part be due to increasing numbers of incidentally detected cancers with new imaging methods. Further, the increase is not only limited to small local tumours but also includes more advanced tumours, which may to some part explain the still high mortality rates. The variation in incidence between populations may have several other explanations. Traditionally the starting point has included thoughts of environmental exposures, which so far have only in part explained the causes of RCC, by means of cigarette smoking and obesity, which may account for approximately 40% of cases in high-risk countries (Table 2). Further, the genetic variations may be of importance as a cause of the difference between populations. Continued research in RCC is needed with the knowledge that nearly 50% of patients die within 5 years after diagnosis. The further search for environmental exposures should take in account the knowledge that RCC consists of different types with specific genetic molecular characteristics. These genetic alterations have in some cases been suggested to be associated with specific exposures. Furthermore, there might exist a modulating effect of genetic polymorphisms among metabolic activation and detoxification enzymes. Hence, a further understanding of the genetic and molecular processes involved in RCC will hopefully give us a better knowledge how to analyse and interpret exposure associations that have importance for both initiation and progression of RCC.