The prognostic relevance of disseminated nodal tumor cells has been demonstrated by several groups. However, their biological behaviour still remains unclear.The aim of the study. Analyse the phenotypic characteristics of disseminated tumor cells in lymph nodes.Material and methods. We established an immuno-enzymatic immuno-gold double-staining technique to simultaneously identify an epithelial antigen as well as the co-expression of plakoglobin, HLA class-I, ICAM-I and Ki-67 on isolated tumor cells. Epithelial cells were marked by the monoclonal antibody Ber-EP4. These results were compared with the corresponding primary tumors.Results. Loss of HLA class-I expression on Ber-EP4+ cells was observed in 33.3% of the patients. ICAM-I neo-expression was detected in 46%, whereas 54% of the cases were ICAM-1 negative. Plakoglobin was expressed in 16% while Ki-67 was detectable only in 5% of the patients. Comparison with the corresponding primary tumors revealed phenotypic alterations of the disseminated cells. In 20% of the cases HLA class-I down-regulation was found, while in 38% plakoglobin was not detectable. In contrast to the primary tumors with a proliferation index of 39%, the nodal Ber-EP4+ cells appeared to be Ki-67 negative in 95% of the patients.Conclusions. Our phenotypic analysis demonstrates that Ber-EP4+ cells in lymph nodes not only display characteristics typical of malignant cells but also phenotypic alterations, in comparison with primary tumors. This is indicative of a selective process which might result in adapted metastatic phenotypes.