The prognosis of renal cell carcinoma (RCC) is generally poor. An easier detection of this tumor and a better monitoring of RCC patients would be possible if serum markers with acceptable sensitivity and specificity were available. In RCC, as opposed to other cancers, no circulating serum markers with sufficient renal specificity have been discovered. In fact, even when the hybridoma technology allowed the production of several monoclonal antibodies against RCC structures, none of them led to any available diagnostic immunoassays. Other possible circulating tumor markers of potential application in RCC patients include different substances such as acute phase reactant proteins, enzymes, mucins, cytokeratins, proteins, interleukins, that demonstrated some relationship with the presence and the changes in the RCC evolution. In this general review we report and discuss the results in the literature obtained by serum assays of these substances which have been shown to be of some help for the prognosis and monitoring of RCC. The greater part of these biomolecules are already measured in clinical practice for the management of other malignancies, but their application in RCC could give interesting clinical information.