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Summary Although the presence of axillary node metastases in breast cancer is a key prognostic indicator and may influence treatment decisions, a significant proportion of patients diagnosed as axillary node negative (ANN) using standard histopathological techniques may have occult nodal metastases (OMs). A combination of limited step-sectioning (4 x 100 /im intervals) and immunohistochemical staining (with cytokeratin (MNF.116) and MUCI (BC2) antibodies) was used to detect OM in a retrospective series of 208 ANN patients. OMs were found in 53 patients (25%), and both step-sectioning and immunohistochemical detection significantly improved detection (P<0.05). Detection using BC2 (25%) was superior to MNF. 116 (18%) and haematoxylin and eosin (H&E) (8%). OMs were found in 51 patients using only the first and deepest sectioning levels and BC2 staining. OMs were more frequently found in lobular (38%) than ductal carcinoma (25%), and more frequently in women less than 50 years (41%) than in older women (19%). Univariate overall and disease-free survival analyses showed that the presence, size and number of OM had prognostic significance as did tumour size (disease-free only) and histological and nuclear grade (P>0.05). Cox multivariate proportional hazard regression analyses showed that the presence and increasing size of OMs were significantly associated with poorer disease-free survival, independently of other prognostic factors (P>0.05). However there was not a significant independent association of the presence of occult metastases with overall survival (P =0.11). These findings have important implications with regard to selection of ANN patients for adjuvant therapy.Keywords: breast cancer; prognosis; occult metastases; detection; mucin Several large clinical trials have illustrated the survival benefits of adjuvant endocrine or chemotherapeutic treatments in patients with axillary node-negative (ANN) breast cancer (Fisher and Redmond, 1992;Stewart, 1992 (Nemoto et al., 1980), yet is has been recognised for some time that a significant proportion of patients diagnosed as node negative using standard histopathological techniques may in fact have nodal metastases. However, the proportion of ANN patients with these occult metastases, the best practical way of detecting them, and the prognostic significance of these metastases remain unclear. There are two main sources of error in the current histopathological examination of axillary lymph nodes for the detection of metastases. The first involves sampling error attributable to the sectioning procedure and is related to the size of the node, the orientation of the node in the sectioning block, the size and location of any metastases, and the number of sections examined (Wilkinson and Hause, 1974). The second involves microscopic misdiagnosis of sectioned metastases, which is related to the size and location of the metastases and the morphology of the lesions and surrounding nodal tissue.Strategies for reducing sectioning error that have been tested include macroscop...

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