Both cryotherapy and thermal ablation are treatment methods for cervical precancerous lesions in screening programs in resource constrained settings. However, for thermal ablation the World Health Organization stated that there is insufficient data to define a standard treatment protocol. This study used an ex-vivo model to compare the tissue interaction of both cryotherapy and thermal ablation to contribute to a treatment protocol. We used porcine tissue to measure the temperature profile over time at 0, 2, 4 and 6 mm depth. For cryotherapy the standard double freeze method was used, thermal ablation was applied for one cycle of 60 s with 100 °C. Based on literature search we used 4 mm depth as landmark for the depth of precancerous lesions, and -10 °C for cryotherapy and 46 °C for thermal ablation as critical temperature to induce cell necrosis. Cryotherapy achieved the critical temperature for tissue necrosis (-10 °C) in 3 out of 6 experiments at 4 mm depth, median minimum temperature was −9.6 °C (IQR 25–75 -15.8 °C to −4.9 °C). Thermal ablation achieved the critical temperature for tissue necrosis (46 °C) in 3 out of 7 experiments at 4 mm depth, median maximum temperature was 43.1 °C (IQR 25–75 42.3 °C to 49.9 °C). Both treatment modalities achieved tissue necrosis at 4 mm depth in our ex-vivo model. For cryotherapy the double freeze technique should be used. For thermal ablation a single application less than 60 s might not be sufficient and multiple applications should be considered.