The standard of care of patients with localized clear cell RCC (ccRCC) is observation after nephrectomy. However, a third of these patients have local or distant recurrence. Along with basic clinical and pathologic variables like stage, necrosis and grade, robust molecular based prognostic markers are needed that could help better predict groups of patients who will most benefit from such adjuvant treatment approaches. ccA/ccB classification was developed to classify ccRCC patients into high and low risk based on gene expression patterns. ClearCode 34 is a genetic signature that was developed from the ccA/ccB classification to predict recurrence in localized ccRCC patients. This signature has been validated in several patient cohorts and is ready for future testing in a variety of clinical scenarios. This review will evaluate the molecular signature ClearCode34, discuss its role in predicting recurrence and consider the rational application of this example of a molecular biomarker in the management of ccRCC.