We have reported that metastatic human melanoma cells utilize the alpha (v)beta3 integrin to adhere to lymph node vitronectin (VN). In the present study, the adhesion of human and rat breast carcinoma cells to lymph node tissue was analyzed. We have previously shown a correlation between the metastatic potential of breast carcinoma cells and an RGD-mediated adhesion to cryostat sections of peripheral lymph nodes; this adhesion could be blocked by an antibody to the integrin beta1 subunit. Here, we show that the metastatic breast carcinoma cells were significantly more adherent to fibronectin (FN) expressed by lymph node-derived stromal cells than non-metastatic cells. Metastatic cells also spread more rapidly than non-metastatic cells on FN-coated substrates. Using a combination of immunofluorescence microscopy, immunoprecipitation and blocking assays with integrin-specific antibodies, we found (i) that expression of the alpha3beta1 integrin on metastatic mammary carcinoma cells was specifically increased in comparison to non-metastatic cells and (ii) that the alpha3beta1 receptor was involved in the increased adhesion of metastatic cells to lymph node FN and in cell spreading on FN-coated substrates. Our data also suggest that the alpha5beta1 integrin, which is also expressed on the metastatic cells, did not contribute to this increase in adhesion. Our data implicate the alpha3beta1 integrin in adhesion to lymph node stromal cell FN and suggest that metastatic cells of different tissue origins (e.g., melanoma and breast carcinoma) may utilize distinct integrin-ligand combinations to colonize the same target organ.