We have found that p53 expression is altered with progression to the metastatic phenotype of a series of neoplastic subpopulations of a single mouse mammary tumor. Single strand conformation polymorphism (SSCP) analysis of p53 transcripts indicate that the expressed p53 genes in each of the subpopulations contain one or more differences from wild type p53. Although the mutations in the coding sequence of p53 are different in each of the sublines, suggesting that independent mutational events have occurred, the mutations are clustered in exons 2-4 and in exon 6. In the metastatic subpopulations, there is either a complete loss of p53 transcriptional activity or accumulation of transcripts with an additional alteration in exons 4-5.