Mutations in oncogenes and tumor suppressor genes in experimental neoplasms in animals and naturally occurring cancers and precursor lesions in humans define and are characterized to define the pathogenesis of specific tumors and to clarify the roles of carcinogenic agents in the progression of neoplasia. We describe here 1) the development of novel techniques to identify gene deletions and point mutations in polymerase chain reaction (PCR) fragments, 2) the roles of activating point mutations in the neu and ras oncogenes in experimental tumor models, and 3) the role of mutational inactivation of the p53 tumor suppressor gene in tumor progression from several rodent tumor models.