The presence of axillary metastases in carcinoma of the breast is of major prognostic significance. The avidin-biotin complex immunohistochemical method was used to determine if a monoclonal antibody cocktail (AE1/AE3) to cytokeratins was as specific and sensitive in detecting metastases as routine light microscopic examination of hematoxylineosin (HE)-stained sections. This study was unique in that identical sections were examined by both standard HE and immunohistochemical methods. Ninety hyperplastic axillary lymph nodes, removed from 14 female patients for a variety of diagnostic reasons, demonstrated no epithelial cells by either technique. Six of 42 nodes removed from five patients with breast cancer and known axillary metastases demonstrated tumor cells when examined with HE, whereas 13 of these nodes demonstrated cytokeratin-positive metastases. The immunohistochemical detection of cytokeratin-positive axillary metastases is both specific and sensitive.