The aim of the present study was to investigate the type of intraglandular spread of lobular neoplasia (LN) and its relationship with invasive lobular carcinoma (ILC) through three-dimensional (3D) stereomicroscopy and analyses of large histological sections (histological macrosections, HM). Fifteen cases showing multiple foci of in situ LN and/or ILC (1 pure LN, 12 LN+ILC, and 2 pure ILC) constituted the basis of the present study. Thirteen cases were treated with mastectomy (including the case of pure LN), and two cases were treated with quadrantectomy. In all cases, large parallel 5-mm-thick sections were embedded in paraffin and stained with hematoxylin and eosin (H&E). Selected large paraffin blocks were investigated with stereomicroscopy. The H&E-stained HM were then compared with the corresponding tissues examined using stereomicroscopy. (1) LN was multicentric in nine cases. (2) The average maximum distance among LN foci was 37.9 mm, while the average maximum distance among ILC areas was 58.2 mm. (3) On 3D examination, LN-filled acini and ducts appeared dilated. When "Pagetoid spread" was present, the ducts were lined by a continuous layer of neoplastic epithelium. (4) No anastomoses between lobes were observed in the two cases where glandular trees were visualized. (5) In 12 cases, ILC areas enveloped ducts and acini affected by LN-an association that was more than coincidental. (6) Multicentric ILC areas not associated with LN indicated vascular spread. It is concluded that the information given in LN and ILC, obtained by analyses of large histological sections, is far superior than that obtained by analyses of conventional histological sections, which underestimate multiple distant small foci of invasion. 3D sections are useful in understanding the architecture of specific lesions.