We studied 23 renal cell carcinomas and two normal kidney tissues by immunohistochemistry using monoclonal antibodies against subunits of the VLA integrins (VLA-1 to VLA-6) and CD51. All integrins investigated in our study, except VLA-4 (ubiquitous negative), were distributed in different patterns in tumors assayed. We found a correlation between VLA-2 expression and site of tissue; primary tumor cells expressed no VLA-2 integrin, whereas tumor cells from metastatic tissues exhibited VLA-2 positivity (P < .009). Additionally, the expression of VLA-3 and VLA-5 correlated with tumor grading; both integrins were undetectable in G1 tumors but widely expressed in G2 and G3 tumors (VLA-3, p < .000; VLA-5, p < .005). Our results suggest that VLA-2 integrin is involved in metastasis of RCC and that poorly differentiated tumor cells have a different integrin phenotype when compared to normal or highly differentiated tumor cells.