Epidemiological and molecular data support the hypothesis that cancer results from a series of acquired somatic mutations. Discovering the initial mutations required for oncogenesis has long been a goal of cancer research. To date, the majority of causative mutations have been identified based on their ability to act in a dominant fashion and/or because they are activated by chromosomal translocations. Forward genetic screens are necessary for unbiased discovery of the remaining unknown oncogenic mutations. Two recent projects have demonstrated the feasibility of using the Sleeping Beauty transposon as an insertional mutagen for cancer gene discovery. In this article we discuss the history of cancer gene discovery and propose novel forward genetic screens using Sleeping Beauty transposon aimed at specific tissues and accelerating the discovery of recessive tumor suppressor genes.