Abnormalities in the p53 tumor suppressor gene have been shown to affect cell cycle control and lead to genetic instability in cell lines of murine and human origin. We have examined genetic instability in 183 primary human breast carcinomas with and without p53 abnormalities. Mutation analysis was performed by constant denaturant gel electrophoresis and DNA sequencing, and abnormal protein expression was examined by immunohistochemical staining methods. Genetic instability was studied by detection of gene amplification, allelic loss, karyotype analysis, and fluorescent in situ hybridization. We found a significant association between p53 abnormalities and genetic instability detected by these methods.