Mutations in the p53 gene are associated with 50% of all cancers and nearly 80% of the p53 mutations are missense changes. We have developed genetic assays based in yeast that can functionally categorize expressed p53 mutant proteins. The combined assays are referred to as the FIP53 system. Because human p53 cDNA can be conveniently cloned in yeast, the FIP53 system provides a rapid and sophisticated system for the functional analysis of p53 mutants. Four categories of mutations have already been identified. The FIP53 system provides the first in vivo battery for tests that can subdivide many p53 mutations that can occur in humans. In particular, the FIP53 system may allow the identification of rare or new alleles that may function better than the wild type.