p53 is a nuclear protein believed to play an important role, through mutation and overexpression, in the progression of human malignant tumors. The authors employed a monoclonal antibody, 1801, and investigated overexpression of p53 in a series of 255 malignant and benign tumors, using deparaffinized sections of methacarn-fixed tissue. Overall, immunohistochemically detected p53 overexpression was found in 39% of malignant tumors, with considerable variation within individual tumor types (34% of breast carcinomas, 92% of ovarian carcinomas, 33% of soft tissue sarcomas). Homogenous, heterogenous, and focal immunostaining patterns were noted. With rare exceptions, no immunostaining of any benign tumors was noted. No immunostaining was found in adjacent, benign tissues, or in a series of fetal tissues. This is the first demonstration of widespread p53 overexpression in alcohol-fixed, embedded tissue and confirms the major role played by p53 in human malignancies.