Potential value of hormone receptor assay in carcinoma in situ of breast. The estrogen receptor (ER) expression of invasive breast cancer has been extensively studied both biochemically and with specific monoclonal antibodies against ER. Relatively few studies have attempted to characterize ER pattern in breast carcinoma in situ (CIS) and in other premalignant lesions. In the current study, the authors investigated the pattern of ER expression in 62 cases of breast CIS, 30 of which had a component of invasive cancer, and 36 cases of atypical hyperplasia. Paraffin sections of formalin-fixed breast tissue underwent enzyme pretreatment to expose nuclear antigenic sites as previously described. Breast tissues then underwent estrogen immunocytochemical assay using specific monoclonal antibodies (Abbott Laboratory, Chicago, IL). The cases were evaluated for heterogeneity, intensity of staining, and percentage of ER-positive cells. An attempt was made to study the relation between the pattern of ER expression, nuclear pleomorphism, and type of CIS. The results of ER immunocytochemical assay showed positive nuclear staining for ER in 75% of the CIS, 73% of CIS with invasive cancer, and 100% of atypical hyperplasias. ER expression in CIS agreed with that in the invasive carcinoma in 29 of 30 cases. This study also suggests that comedocarcinoma has a higher incidence of negative ER expression than the other types of CIS, particularly when it is associated with significant nuclear pleomorphism. There was no significant difference in ER tumor heterogeneity between premalignant and malignant lesions. 