The aim of this study was to evaluate the prognostic information of soluble carbonic anhydrase (CA) IX expression in renal cell carcinoma (RCC). Serum CA IX was analysed in 361 patients. Tumour type, TNM stage, nuclear grade, and RCC-specific survival were assessed. Serum and immunohistochemical expression were compared. Median serum CA IX expression was 141 (range 2-4, 181) pg/ml. Levels were significantly higher in 287 patients with clear cell, compared to 40 papillary (p<0.001) and 22 oncocytoma (p=0.002), but not to 12 chromophobe RCC (p=0.35). Serum CA IX in clear cell RCC was positively correlated to TNM stage (p=0.002). There was a positive trend between serum and immunohistochemical CA IX expression. In a multivariate analysis of clear cell RCC, TNM stage and nuclear grade were independent prognostic factors. Serum CA IX was higher in clear cell RCC compared to other RCC types. In clear cell RCC, serum CA IX correlated to TNM stage, but not survival.