One particular challenge in the treatment of kidney tumors is the range of histologies and tumor phenotypes a renal mass can represent. A kidney tumor can range from benign (eg, oncocytoma) to a clinically indolent malignancy (eg, papillary type I, chromophobe) to aggressive disease [eg, papillary type II or high-grade clear cell renal cell carcinoma (ccRCC)]. Even among various subtypes, kidney cancers are genetically diverse with variable prognoses and treatment response rates. Therefore, the key to proper treatment is the differentiation of these subtypes. Currently, a wide array of diagnostic, prognostic, and predictive biomarkers exist that may help guide the individualized care of kidney cancer patients. This review will discuss the various serum, urine, imaging, and immunohistological biomarkers available in practice.