Retroviruses are powerful insertional somatic mutagens that have been used for many landmark discoveries of cancer genes in model organisms. However, their use as a cancer gene discovery tool has been limited to only a few tissues, mainly the hematopoietic system and mammary gland. Recently, the Sleeping Beauty (SB) transposon system was shown to be useful for random somatic cell mutagenesis in mice, allowing the induction or acceleration of tumor formation both in the hematopoietic system and in sarcomas. In these tumors, SB transposons repeatedly "tagged" specific genes, both known and new cancer genes. These results indicate that the SB system has great potential both for generating specific mouse models of human cancer and for cancer gene discovery in a wide variety of tissues.