Renal tumors, in particular clear cell renal cell carcinomas, have an unclear prognosis and metastatic potential. Cell cycle regulators play a key role in cellular proliferation and have been implicated in neoplasia. The cell cycle inhibitor p27 has been associated with prognosis in various tumor types. Recently a reported association between p27 and Von Hippel-Lindau (VHL) gene function has also been noted. We have examined p27 and VHL expression by immunohistochemistry in a panel of kidney tumors and have noted specific and unique patterns of p27 expression in various tumor types. In addition, we have analyzed p27 expression in clear cell type renal cell carcinomas and have noted a significant association between decreasing p27 expression and increasing tumor size, suggesting a relation between renal cell proliferation and loss of p27 function. These findings suggest a role for p27 in the development of various types of renal tumors.