With the advent of newer molecular technologies, our knowledge of cellular mechanisms with tumors of the kidney and testis has grown exponentially. Molecular technologies have led to better understanding of interplay between the von Hippel-Lindau gene and angiogenic cytokines in renal cancer and isochromosome 12p in testicular neoplasms. The result has been development of antiangiogenic-targeted therapy within recent years that has become the mainstay treatment for metastatic renal cell cancer. In the near future, classification and diagnosis of renal and testicular tumors through morphologic analysis will be supplemented by molecular information correlating to prognosis and targeted therapy. This article outlines tumor molecular pathology of the kidney and testis encompassing current genomic, epigenomic, and proteonomic findings.