Regressive changes (RC) have been described in malignant melanoma, carcinomas of the prostate and cervix. The presence of RC in these neoplasms may signify some degree of host response to tumor and seems to be a sign of poor prognosis for some neoplasms. RC in breast cancer is vaguely defined in the older literature. We have observed periodically similar RC in a subset of high-grade ductal carcinoma in situ (HGDCIS) in breast specimens. The aim of our study is to demonstrate how to recognize RC in the diagnostic setting and an attempt to understand the biologic behavior in this subset of HGDCIS cases. Fifty-nine cases of HG-DCIS (35 cases with RC and 24 cases without RC) were included. We defined RC in our study as demonstrating thick periductal fibrosis, dense lymphocytic infiltrate, and a thin rim of intact neoplastic cells. A short panel of immunomarkers to study this entity included myoepithelial markers. Reduced expression of myoepithelial markers (p63 and smooth muscle heavy chain myosin) were seen more frequently in the HGDCIS group with RC than without RC cases. Invasion as well as metastatic disease was seen in association with HGDCIS with RC nearly 4 times as often. It is also critically important to recognize HGDCIS-RC for diagnostic purposes, as the differential diagnosis of RC includes, benign associations such as papilloma, fibrocystic changes and periductal mastitis. HGDCIS-RC may also be a sign of an aggressive phenotype than other HGDCIS subtypes. Further outcome studies are necessary to determine if it has a clinical impact akin to other tumors with RC.