RF ablation uses RF current to heat and kill cancer applied via an electrode inserted under image guidance. Tumor has about half the electrical resistivity of normal tissue below 20 kHz, but similar resistivity above 500 kHz. We placed normal porcine liver tissue in contact with agar gel having similar resistivity as tumor within 20-450 kHz. A needle electrode was placed with half of the electrically active tip in each layer. We performed ablation with electric current applied for 12 min at 30 W, either at 20 or 450 kHz (n = 7 each), while measuring temperature via thermocouples 4 and 8 mm from the electrode. Mathematical heat-transfer models were created of an equivalent configuration and temperature profile determined at both frequencies. At 8-mm distance, at 450 kHz, tumor gel phantom and normal tissue obtained similar temperatures (57.5 ± 1.4 versus 58.7 ± 2.5 °C); at 20 kHz, tumor phantom obtained significantly higher temperatures than normal tissue (65.6 ± 2.0 versus 57.2 ± 5.6 °C, p <; 0.01). Computer models confirm these results, and show the ablation zone diameter to be larger within the tumor phantom at 20 kHz compared to 450 kHz. Heating at low RFs may thus allow targeted heating of tumor tissue and reduced heating of normal tissue.