During 2007-2008, three new human polyomaviruses, KI, WU and Merkel cell cancer polyomaviruses have been discovered, of which the latter has also been identified in a human tumour. This development revives the interest in both human and animal polyomaviruses and their potential role in tumour development and disease particularly in immune suppressed individuals. Murine polyomavirus (MPyV) has in the past been used for acquiring knowledge of transformation mechanisms in vitro, as well as in immunological studies with regard to virus-induced tumour development in the natural host of the virus. Here we summarize some of the accumulated knowledge achieved in the MPyV field in view of the balance between tumour virus, the immune system and tumour development, and discuss this in relation to infections with human polyomaviruses. We also present how virus-like particles (VLPs) and gluthatione-S-transferase VP1 can be used for vaccination against the same tumour virus not only in mice with a well-functioning immune system, but also in immune suppressed mice.