The distinction between lobular neoplasia and infiltrating lobular carcinoma from ductal neoplasia and infiltrating duct carcinoma with equivocal histologic features may present a challenge as this distinction has important therapeutic implications. Although E-cadherin staining has been of value in helping to make this determination, the variability of the E-cadherin staining pattern and the immunohistochemistry techniques can be problematic in clinical practice. A total of 161 cases of breast lesions previously diagnosed as lobular neoplasia and infiltrating lobular carcinoma were selected from the departmental files. Three surgical pathologists interpreted them in a blinded manner for the histology diagnoses and E-cadherin staining. E-cadherin staining was conducted on the paraffin-embedded sections of the breast lesions using two different source antibodies. Our results using morphology and E-cadherin stain agreed with the previous diagnoses of lobular neoplasia and infiltrating lobular carcinoma in 140 of 161 cases (86.9%). Among the 140 cases, three pathologists agreed with the morphologic diagnoses of lobular neoplasia and infiltrating lobular carcinoma in 100 (71.4%), two pathologists in 26 (18.6%) and one pathologist in 14 (10%). All three pathologists disagreed with the previous diagnoses of lobular neoplasia and infiltrating lobular carcinoma but reevaluated as ductal lesions in 21 cases (13.0%). E-cadherin staining was confirmatory in 136 of total 161 cases (84.5%) of both lobular and duct lesions by showing the loss of staining in lobular lesions and the presence of complete membrane staining in duct lesions. Aberrant E-cadherin reactions were retained weak or partial incomplete thin membrane reaction in lobular-type lesions and reduced membrane reaction in ductal-type lesions were seen in 25 of the total 161 cases (15.5%). E-cadherin immunoreaction with two different antibodies showed discrepant results in 5 of 78 cases tested (6.4%). This study illustrates (1) interobserver variability of the morphologic diagnoses of lobular neoplasia/infiltrating lobular carcinoma and duct neoplasia/infiltrating duct carcinoma, (2) the occasional presence of aberrant E-cadherin stain pattern in these breast lesions and (3) variability of E-cadherin immunostaining results by two different antibodies.