Renal neoplasms exhibit a wide spectrum of molecular characteristics that are closely associated with their diverse morphologic manifestations and clinical behaviors. A wealth of information has been garnered via methodology ranging from classical cytogenetics to FISH and gene expression profiling; however, the exact mechanisms by which each type of renal tumor develops remain incompletely understood. Oddly, tumors with distinctly different morphology and prognosis sometimes show some overlap in the observed genetic abnormalities; by contrast, morphologically well characterized benign and malignant tumors that seem intuitively related cannot necessarily be shown to exhibit a step-wise progression from benign to malignant biologic behavior. Nevertheless, modern methodologies have been highly successful, not only in subclassifying renal tumors, but also in defining previously unrecognized entities. Further avenues of utility for these methods probably include the resolution of challenging differential diagnoses, as well as application in targeted therapy and prediction of outcome. We review the molecular and genetic characteristics of renal neoplasms, with emphasis on markers that demonstrate utility in differentiating morphologically similar neoplasms and in predicting clinical outcome.