The present review focuses on diagnostic approaches to identify patients with minimal residual epithelial cancer. Epithelial malignancies are the most common forms of cancer in Western industrialized countries. The failure to decrease the mortality of patients with epithelial tumors is most likely due to early dissemination of cancer cells to secondary sites, which is usually missed by conventional diagnostic procedures used for tumor staging. Therefore, over the past ten years sensitive assays have been developed to detect individual carcinoma cells disseminated to regional lymph nodes or distant organs. Among the distant organs, bone marrow has appeared as the most important indicator site where hematogeneously spread cancer cells can be detected. With regard to detection techniques, most investigators have used either immunocytochemical assays or molecular methods based on the polymerase chain reaction (PCR). Monoclonal antibodies to a variety of ‘epithelial-specific’ cytoskele-ton and membrane antigens have been applied in immunocytochemical assays. At present, antibodies to cytokeratins can be regarded as the most specific and sensitive probes to detect isolated epithelial tumor cells in bone marrow. However, in lymph nodes the detection of disseminated epithelial cells is hampered because of the expression of cytokeratins by lymphatic reticulum cells. Presently PCR-based methods are applied to detect tumor-associated mutations of the ki-ras and p53 genes, or mRNA from ‘tissue-specific’ genes. Thus far, almost all data on the prognostic significance of microdisseminated cells are based on immunocytochemical analyses, whereas the molecular genetic assays still need to be validated in clinical trials. In order to introduce the available methods into international tumor classifications, standardized protocols need to be developed and validated in multicenter studies.