We report two cases of spontaneous regression of multiple pulmonary metastases occurring after radiofrequency ablation (RFA) of a single lung metastasis. To the best of our knowledge, these are the first such cases reported. These two patients presented with lung metastases progressive despite treatment with interleukin-2, interferon, or sorafenib but were safely ablated with percutaneous RFA under computed tomography guidance. Percutaneous RFA allowed control of the targeted tumors for >1 year. Distant lung metastases presented an objective response despite the fact that they received no targeted local treatment. Local ablative techniques, such as RFA, induce the release of tumor-degradation product, which is probably responsible for an immunologic reaction that is able to produce a response in distant tumors.