When a vaccine-elicited immune response is directed against oncoantigens--proteins required for the neoplastic process--the chance that the tumour will evade the vaccine should be reduced. But how can these causal oncoantigens be identified? One approach is to find tumour-associated and microenvironment-associated oncoantigens required for progression from one tumour stage to the next by comparing gene signatures isolated from the different stages of tumour progression in cancer-prone transgenic mice. Mouse oncoantigens subsequently shown to be involved in human cancer can then be validated in mouse vaccination experiments. This provides the groundwork for the rational design of cancer vaccines for clinical trials.