Introduction: We investigated whether CA9 protein could be used as a prognostic tumor marker as well as a diagnostic biomarker in renal clear cell carcinoma. Materials and Methods: Nephrectomy specimens from 92 patients were used in this study. 80 of these were renal cell carcinomas, 10 adenomas and 2 oncocytomas. Of the renal cell carcinomas, 67 were clear cell carcinomas. immunohistochemical analysis using CA9 monoclonal antibody (M75) was performed on paraffin-em bedded specimens. CA9 staining was correlated with tumor stage, grade, lymph node involvement, distant metastasis and cumulative survival time. Results: CA9 was present in 91.2% of clear cell carcinomas. Low staining was a poor prognostic factor, and conversely high staining a good prognostic one. CA9 expression was found to be the best prognostic factor when compared with T stage and grade. Even in low-grade and stage tumors, the presence of low expression correlated with lowered survival times. Conclusions: On the basis of our study, CA9 is a significant molecular marker in renal clear cell carcinomas. Decreased CA9 expression is independently associated with poor survival. CA9 can be used to predict clinical outcome and identify high-risk patients in need for adjuvant immunotherapy and CA9 targeted therapies. Copyright (C) 2005 S. Karger AG, Basel.