Large histologic sections (LHSs) are increasingly used in the study of normal and neoplastic breast tissue. LHSs allow the direct visualization of a large part of the breast glandular tree. Accordingly, LHSs have shown that in situ and invasive lobular carcinoma is a multilobar (and hence multifocal) neoplastic lesion in more than 50% of the cases, and that poorly differentiated duct carcinoma in situ (DCIS grade 3) is frequently unifocal, whereas it is often multifocal when the in situ lesion is a well-differentiated type (DCIS grade 1). Forty-five mastectomies were studied with large sections. Mastectomies were performed when quadrantectomy did not guarantee radical excision of the tumor with adequate cosmesis because of the large size of the lesion or because the neoplastic lesion was located below the nipple. Excluded were cases of lobular neoplasia or invasive lobular carcinoma, because they were reported separately, and cases of mastectomies performed for sarcoma or recurrent phyllodes tumor. All cases had undergone a preoperative diagnostic procedure (fine needle aspiration), and the relative positive material was reviewed. All 45 cases showed in situ duct carcinoma and 37 showed evidence of invasive duct carcinoma. Forty-two cases of DCIS were multifocal, whereas only 4 invasive duct carcinoma were shown as multifocal. When DCIS lesions were subdivided into 3 grades, no statistical significance was seen among the 3 groups of DCIS in regard to multifocality. Nevertheless, DCIS grade 1 was a widespread condition involving more than one lobe and quadrant, whereas DCIS grades 2 and 3 appeared more localized. DCIS grade 1 was more similar to that previously observed in lobular in situ neoplasia/lobular in situ carcinoma. In 66.6% of the cases, DCIS foci were found within the invasive areas, indicating a more than fortuitous occurrence (2-sided P=.0357).