beta 2-microglobulin (beta 2m) content and distribution in human benign and malignant breast tissues have been investigated by immunohistologic means, and wide differences in the expression of this protein have been observed. The distribution of beta 2m as determined by indirect immunofluorescence was uniform throughout normal human and benign breast tumor tissues, as well as in human tumor xenografts grown in athymic mice, but marked difference in beta 2m content was demonstrated between individual tumors. In breast carcinomas, heterogeneity in beta 2m expression was found to exist within individual tumors. This heterogeneity was evident mainly in moderately well-differentiated tumors; the majority of poorly differentiated tumors did not express beta 2m at all. It is suggested that the expression of surface beta 2m is an indicator of tumor cell differentiation or maturation.