Abstract: Methods for generating a prognostic signature for a subject with clear cell renal cell carcinoma (ccRCC) are disclosed. The methods include determining expression levels for three or more genes disclosed in ccRCC cells obtained from the subject, wherein the determining provides a prognostic signature for the subject. Also provided are methods for assessing risk of an adverse outcome of a subject clear cell renal cell carcinoma (ccRCC), method for predicting a clinical outcome of a treatment in a subject diagnosed with clear cell renal cell carcinoma (ccRCC), and arrays that include polynucleotides that hybridize to at least three genes disclosed or that include specific peptide or polypeptide gene products of at least three of the genes disclosed.