Summary 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 54kd 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.Prognosis and treatment of breast cancer is heavily influenced by the detection of metastases in lymph nodes. Foci formed by clumps of cells are easily spotted in standard histological sections, but a more difficult task is the detection of metastatic foci of one or few cells spread within a tissue.In as many as 24% of lymph nodes reported free of metastases by standard histological examination, various authors found metastases when multiple or serial sections were cut (Pickren, 1961;Fisher et al., 1978b). Immunological markers also improve the specificity and accuracy of cell detection, therefore it is important to evaluate their usefulness in improving standard histological procedures.Wells et al. (1984) utilizing 3 monoclonal antibodies found micro-metastatic foci in about 20% of lymph nodes from 45 cases of ductal or lobular breast cancer reported negative on conventional histology. On the contrary Sloane et al. (1980) reached the conclusion that detection of metastases in lymph nodes was not improved by immunocytochemistry. However they used a polyclonal antiserum against fat globule membranes of human milk.In this study 50 cases of infiltrating lobular carcinoma of the breast reported to have axillary lymph nodes free of metastases were re-examined to determine whether occult metastases were revealed