The Lewis blood group antigens (Lewis-a [Le(a)] and Lewis-b [Le(b)]) and their precursors are present on various normal human epithelial cell surfaces. The authors examined 35 benign and malignant human breast lesions using mouse monoclonal antibodies to synthetic Le(a) and Le(b) carbohydrate antigens. Normal breast lobular and ductal epithelium and benign breast lesions showed Le(b) staining but only occasional Le(a) staining. In invasive ductal carcinomas of breast, of all grades, a loss of Le(b) antigen staining was found in 80% of the breast cancer cases. This reduced Le(b) antigen expression increased with the grade of malignancy. Therefore, the loss of Le(b) blood group antigens on breast cancer cell surfaces may suggest altered fucosylation patterns in malignant cells and reflect the degree of malignancy and/or invasiveness.