Eleven surgical pathologists studied microscopic sections from 45 mastectomy specimens of node positive breast cancer patients who had been entered into ECOG clinical trials. Inter-observer reproducibility for histoprognostic features was examined as a prerequisite before a subsequent evaluation of their possible clinical applicability could be undertaken. Histological type, nuclear grade, tubular formation, and lymphoid reactions were studied in the cancerous tissues. Lymph nodal responses (follicular and pulp prominence, sinus histiocytosis) were also examined in a manner that stimulated slide review in routine surgical pathology practice. Numerous two-way comparisons of the pathologists' findings resulted in low levels of agreement (usually much less than 90%). The degree of inter-observer reliability is clinically unacceptable using customary slide review analysis. New ways of examining breast cancer tissues need to be explored in the search for prognostic features which can be applied to the clinical management of breast cancer patients.