The role played currently by the different ancillary diagnostic techniques in the diagnosis of adult epithelial renal tumors continues to be debated. It has also become clear that in some instances light microscopic appearance alone cannot be used to classify these neoplasms into specific categories with the degree of precision required for therapeutic purposes. Renal cell carcinoma (RCC) subtypes may share common histologic characteristics but exhibit different biological behavior and response to therapy which clearly indicates the crucial role that advanced pathologic speciation plays in the current assessment of these neoplasms. Although immunohistochemistry is widely used for the purpose of categorizing renal tumors because of its widespread availability, the immunoprofiles of the various types of renal neoplasms overlap significantly, making definitive diagnostic determinations difficult and challenging at times. This manuscript will address how ancillary diagnostic techniques can be incorporated into the routine evaluation of neoplastic renal masses to improve classification. Both cytology and surgical specimens will be addressed, as fine needle aspiration (FNA) is being used with preference in many cases in the diagnosis of renal masses. Surgical and cytopathologists must intelligently select the ancillary diagnostic technique/s that will provide the information needed to solve the differential diagnosis under consideration in a given case. However, in some cases >1 of these techniques should be used to make an accurate diagnosis with the aim of arriving at an unequivocal diagnosis. The identification of specific signaling pathways that are defective in certain types of renal neoplasms has made possible the design of target-specific therapies that are directed towards the aberrant pathways associated with the defective proteins found in these tumors. This makes the exact classification of these neoplasms and the detection of these aberrant proteins targeted for treatment an absolute requirement for the application of these molecular-based therapeutic interventions. The role that the pathologic assessment plays in the classification of renal tumors becomes more important than ever to take advantage of this and similar new molecular-oriented therapies.