Purpose: To determine the feasibility of percutaneous microwave coagulation (PMC) for the treatment of small solitary breast cancers. Materials and Methods: With approval of the institutional ethics committee and written informed consent, 41 patients with core-needlebiopsy-proved breast cancers 3.0 cm or less in diameter accessed by using ultrasonography (US) were recruited. US-guided PMC was performed with general anesthesia, followed immediately by mastectomy. Histochemical staining with α-nicotinamide adenine dinucleotide, reduced (NADH)-diaphorase was used to determine cell viability and the extent of PMC lesions. Results: The mean tumor volume was 5.26 cm 3 ± 3.80 (standard deviation), with a range from 0.09 to 14.14 cm 3. PMC was successfully performed in all cases, with complete tumor ablation as assessed by using US. The mean time to reach complete ablation was 4.48 minutes, ranging from 3 to 10 minutes. With microscopic examination, 37 of 41 cases (90%; 95% confidence interval [CI]: 76.9%, 97.3%) showed complete tumor coagulation, as observed by using α-NADH-diaphorase staining. Of 38 cases diagnosed with invasive ductal carcinoma, 36 cases (95%; 95% CI: 82.3%, 99.4%) showed complete tumor coagulation. Slight thermal injuries to the skin and pectoralis major muscle, which proved reversible, were found in three cases. Conclusion: US-guided PMC of small solitary breast cancers is feasible. Nevertheless, larger-scale clinical trials are still needed to validate PMC for adoption into a standard clinical practice. © RSNA, 2012.