Renal tumors are classified into histopathologic subtypes based on light microscopy. Classification is important because subtypes have distinct genetic abnormalities and clinical behavior, yet is difficult because many cases have heterogeneous morphology. Thus, several molecular assays have been developed for tumor classification. Immunohistochemistry (IHC) permits correlation of molecular data with tissue morphology, but is difficult to quantify or perform in multiplex. Quantitative RT-PCR and gene expression microarrays are more quantitative, but lose morphologic information. We hypothesize that direct integration of histopathology with nanomolecular expression profiling will provide sensitive and specific data for renal tumor classification. Thus, we are developing novel IHC assays using antibodies conjugated to nanoparticle tags with surface-enhanced Raman scattering properties (SERS). Our preliminary data suggests that SERS-IHC can be performed using standard microscopic equipment, with potential for sensitive, quantitative multiplex assays on fixed tissues.