The majority of immunosuppressive agents used to prevent rejection in transplant patients have also been shown to increase malignancy risk. Renal transplant patients are dependent upon their solitary allograft kidney in order to remain dialysis free, and the discovery of a primary malignancy within the allograft poses a therapeutic dilemma. We describe two cases of primary renal allograft malignancies and discuss nephron-preserving surgical treatment. Furthermore, we discuss the potential anti-tumor role of the immunosuppressive agent sirolimus in the treatment of these complex patients.