Our objective was to assess the loss of E-cadherin (EC) as a diagnostic marker or a predictor of prognosis. We stained 276 breast carcinomas with monoclonal antibodies to EC (invasive lobular carcinomas [ILC] and variants, 59; invasive ductal carcinoma and ductal special types [IDC], 204; tubulolobular carcinoma [TLC], 4; and invasive carcinoma [IC], uncertain whether lobular or ductal type, 9). The results were as follows: EC+IDCs, 99.5%; EC-ILCs, 90%; EC+ILCs, 10%; EC+pleomorphic ILCs, 20%; EC-ICs, 44%. All 4 TLCs showed positive tubules while cords were negative. Statistically a correlation of EC loss with a positive diagnosis of ILC was found but there was no correlation with any prognostic tumor variables. A negative EC stain confirms the diagnosis of ILC (specificity, 97.7%; negative predictive value, 96.8%; sensitivity, 88.1%; positive predictive value, 91.2%). EC is helpful in classifying cases with indeterminate histologic features. EC loss is uncommon in nonlobular carcinomas with no correlation to currently established prognostic variables.