Conventional renal cell carcinomas (CRCCs) were investigated for the expression of annexin II (ANX II) to determine out whether this calcium-binding protein could serve as a useful prognostic marker. CRCCs and adjacent nonneoplastic tissue from 33 patients were investigated for ANX II by immunohistochemistry, RT-PCR, and western blot analysis. ANX II expression was correlated with tumor differentiation (Fuhrman grade) and to clinical outcome. Tumors were composed of ANX II positive and negative cells. In grade I tumors only a weak membranous staining was seen in immunopositive cells. In grade II and III tumors, however, ANX II was seen in the cytoplasm and at the cell membranes of tumor cells. On serial sections membranous and cytoplasmic immunoreactivity for ANX II occurred predominantly in eosinophilic cells whereas clear cells were mostly immunonegative. The ANX II expression in CRCCs was correlated with clinical outcome and Fuhrman grade. Since ANX II expression is correlated with Fuhrman grade and clinical outcome it may be a useful marker for prognosis in CRCC.