Immunological markers improve specificity and accuracy of cell detection, therefore it is important to evaluate their usefulness in improving standard histological procedures. This study investigates whether immunocytochemical techniques increase the accuracy of detection, in axillary lymph nodes, of metastatic cells from infiltrating breast lobular carcinoma (ILC). Fifty cases of ILC reported to be node-negative were selected. New serial sections were cut from a total of 767 lymph nodes, stained with H&E and tested in immunoperoxidase (ABC procedure) with a conventional anti-Epithelial Membrane Antigen (EMA) serum, with a monoclonal raised against human milk fat globule membranes (HMFG-2) and with a monoclonal against 54 kd keratin. Metastases were detected immunocytochemically in 12 cases (24%); in five of these cases metastatic cells were also visible in serial H&E sections. Monoclonals offered no evident advantage over anti-EMA conventional antiserum. Immunocytochemical positivity alone is not sufficient evidence for metastatic invasion since macrophages occasionally appear EMA- and HMFG-2-positive (probably because of secondary incorporation of the antigen), and so an improvement in the accuracy of breast cancer metastatic cell detection in axillary lymph nodes requires a combined histo-immunological approach.