Background and Purpose: Small renal tumors are often serendipitously detected during the screening of patients for renal or other disease entities. Rather than perform a radical or partial nephrectomy for these diminutive lesions, several centers have begun to explore a variety of ablative energy sources that could be applied directly via a percutaneously placed needle-like probe. To evaluate the utility of such treatment for small renal tumors/masses, we compared the feasibility, regularity (consistency in size and shape), and reproducibility of necrosis produced in normal porcine kidneys by different modes of tissue ablation: microwaves, cold impedance-based and temperature-based radiofrequency (RF) energy (monopolar and bipolar), and chemical. Chemoablation was accomplished using ethanol gel, hypertonic saline gel, and acetic acid gel either alone or with simultaneous application of monopolar or bipolar RF energy. Materials and Methods: A total of 107 renal lesions were created laparoscopically in 33 domestic pigs. Microwave thermoablation (N = 12) was done using a Targis T3 (Urologix) 1OF antenna. Cryoablation (N = 16) was done using a single 1.5-mm probe or three 17F microprobes (17F SeedNet™ system; Galil Medical) (N = 10 single probe and N = 6 three probes); a double freeze cycle with a passive thaw was employed under ultrasound guidance. Dry RF lesions were created using custom-made 18-gauge single-needle monopolar probe with two or three exposed metal tips (GelTx) (N = 12) or a single-needle bipolar probe (N = 6) at 50 W of 510 kHz RF energy for 5 minutes. In addition, a multitine RF probe (RITA Medical Systems) was used in one set of studies (N = 6). Both impedance- and temperature-based RF were evaluated. Chemoablation was performed with 95% ethanol (4 mL), 24% hypertonic saline (4 mL), and 50% acetic acid (4 mL) as single injections. In addition, chemoablation was tested with monopolar and bipolar RF (wet RF). Tissues were harvested 1 week after ablation for light microscopy. Results: In 11 of the 15 ablation techniques, there was complete necrosis in all lesions; however, three ethanol gel lesions had skip areas, three hypertonic saline gel lesions showed no necrosis or injury, and one monopolar RF and one bipolar RF lesion showed skip areas. In contrast to impedance-based RF, heat-based RF (RITA) caused complete necrosis without skip areas. All cryolesions resulted in complete tissue necrosis, and cryotherapy was the only modality for which lesion size could be effectively monitored using ultrasound imaging. Conclusions: Cryoablation and thermotherapy produce well-delineated, completely necrotic renal lesions. The single-probe monopolar and bipolar RF produce limited areas of tissue necrosis; however, both are enhanced by using hypertonic saline, acetic acid, or ethanol gel. Hypertonic saline gel with RF consistently provided the largest lesions. Ethanol and hypertonic saline gels tested alone failed to produce consistent cellular necrosis at 1 week. In contrast, RITA using the Starburst™ XL probe produced consistent necrosis, while impedance-based RF left skip areas of viable tissue. Renal cryotherapy under ultrasound surveillance produced hypoechoic lesions, which could be reasonably monitored, while all other modalities yielded hyperechoic lesions the margins of which could not be properly monitored with ultrasound imaging.