E-cadherin (E-CD) is an epithelial-specific cell adhesion molecule, whose expression is lost in invasive lobular (ILC) but not in invasive ductal carcinoma (IDC) of the breast. This cell adhesion system can be disrupted by tyrosine kinase c-erbB-2/HER-2/neu. We examined 106 cases of high-grade invasive breast cancer, including 91 IDCs, 12 ILCs and 3 pleomorphic lobular carcinomas (PLCs). We determined Nottingham histological grade and performed immunohistochemistry for estrogen and progesterone receptors (ER/PR), Ki-67, E-CD and c-erbB-2/HER-2/neu with subsequent fluorescence in situ hybridization. Amplification of c-erbB-2/HER-2/neu gene was observed in 55/91 (60.4%) of IDCs, 3/12 (25%) of ILCs and 1/3 (33.3%) of PLCs, and associated with positive axillary lymph nodes. E-CD expression was lost in 14/91 (15.4%) of IDCs, 10/12 (83.3%) of ILCs and 2/3 (66.7%) of PLCs. The loss of E-CD immunoreactivity in IDCs appeared to be associated with c-erbB-2/HER-2/neu gene amplification, negative ER/PR status and positive lymph nodes, whereas E-CD-positive ILCs tended to be HER-2/neu-positive. The biological significance of E-CD expression seems to be different in high-grade IDC and ILC. Oncogenic pathway mediated by c-erbB-2/HER-2/neu may affect the E-CD expression in most invasive ductal breast carcinomas in vivo.