Recent research on genetic alterations found in human cancers has shown that inactivation of a tumor suppressor gene is a major step in the development of cancers. Two strategies have so far been widely used to study tumor suppressor genes in clinical materials: screening with antibodies and DNA structure-based screening. Recently, a different approach based on a biological assay for tumor suppressor gene function has been devised by using yeast as a living test tube. This method takes advantage of the fact that gapped plasmid is repaired by homologous recombination between the linear plasmid and DNA fragment in yeast. The yeast assay in which yeast change color according to the status of tumor suppressor gene raises the very real possibility of simple and large-scale screening for the genetic mutations in clinical samples. We describe here two conceptually different yeast assays: p53 yeast functional assay and APC premature termination assay.