One hundred and eighty-eight infiltrating ductal carcinomas of the breast were examined immunohistochemically (IMM) for p53, and the results were compared to those of single strand conformation polymorphism (SSCP). Of the 65 IMM+ cases (35%), 32 showed a genetic alteration in exons 5 to 9. In some of the IMM+ SSCP- cases, the number of 53+ cells in the tumor was too low to be detected by SSCP. Cases with only a few p53+ cells must not necessarily be considered negative, because a genetic alteration has been found in nine such cases. However, in a few cases, the accumulation of p53 protein could be caused by a factor other than mutation. Of the 123 IMM- cases, six showed gene polymorphism. p53 phenotype, as established with three monoclonal antibodies, did not correlate with genetic alteration in a particular exon. p53 IMM+ or SSCP+ tumors were generally ER-, grade III tumors and were uncommon in women older than 69 yr of age. The two methods have almost the same prognostic value. The accumulation of p53 protein is a good indicator of p53 mutation and therefore, immunohistochemistry remains a good method for the detection of such mutations.