Background: With recent improvements in breast imaging, our ability to identify small breast tumors has markedly improved, prompting significant interest in the use of ablation without surgical excision to treat early-stage breast cancer. We conducted a multi-institutional pilot safety study of cryoablation in the treatment of primary breast carcinomas.Methods: Twenty-nine patients with ultrasound-visible primary invasive breast cancer Յ2.0 cm were enrolled. Twenty-seven (93%) successfully underwent ultrasound-guided cryoablation with a tabletop argon gas-based cryoablation system with a double freeze/thaw cycle. Standard surgical resection was performed 1 to 4 weeks after cryoablation. Patients were monitored for complications, and pathology data were used to assess efficacy.Results: Cryoablation was successfully performed in an office-based setting with only local anesthesia. There were no complications to the procedure or postprocedural pain requiring narcotic pain medications. Cryoablation successfully destroyed 100% of cancers Ͻ1.0 cm. For tumors between 1.0 and 1.5 cm, this success rate was achieved only in patients with invasive ductal carcinoma without a significant ductal carcinoma-in-situ (DCIS) component. For unselected tumors Ͼ1.5 cm, cryoablation was not reliable with this technique. Patients with noncalcified DCIS were the cause of most cryoablation failures.Conclusions: Cryoablation is a safe and well-tolerated office-based procedure for the ablation of early-stage breast cancer. At this time, cryoablation should be limited to patients with invasive ductal carcinoma Յ1.5 cm and with Ͻ25% DCIS in the core biopsy. A multicenter phase II clinical trial is planned.