Cryotherapy is a form of thermal therapy for the treatment of small renal masses, particularly in high-risk patients. However, optimal application and the critical temperature for in vivo cell death have not been well established. Additionally, most centers do not currently monitor temperature during the procedure. Using in vitro gel, ex vivo porcine kidney, and in vivo porcine kidney models, we have demonstrated with both of the commercially available cryotherapy units that tissue temperatures are variable and that gel, while providing reproducible isotherms, is not an accurate model for temperature planning in vivo, likely because of the heat sink effect of highly vascular renal tissue. Placing the cryoprobes through and slightly beyond the tumor and using multi-point temperature sensing probes is recommended to improve the accuracy of the procedure.