Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. Early diagnosis is associated with favorable prognosis. There are currently no biomarkers to enable early diagnosis and patients are often diagnosed at late stage when chances of survival are dismal. Moreover, the prognosis of RCC is variable and there are no prognostic markers. We are using biomarker discovery approach that starts with biomarker identification by tissue proteins. Our specific and quantitative approach has been proven successful for biomarker identification in many cancers. Early diagnosis will have a great impact on patient care since it will significantly reduce the risk of complications of late stage disease, and will also lead to significant reduction in the cost of treating advanced metastatic disease. Moreover, we will be able to identify molecular markers that can accurately distinguish between RCC subtypes, leading to personalized medical care. This is superior to the current distinction that relies on morphology alone. Furthermore, treatment of metastatic RCC is clinically challenging as often times only a subset of patients will respond to treatment. There are no biomarkers available to predict recurrence of RCC. The identification of prognostic markers for RCC patients will allow for more effective and individualized patient management. Although few genetic abnormalities have been identified, RCC pathogenesis remains to be elucidated. Bioinformatic analysis of dysregulated proteins in RCC will shed light on the pathways that contribute to this malignancy leading to a further understanding of RCC carcinogenesis and forming the foundation to design new therapies.