This study was conducted to evaluate the safety and efficacy of ultrasound (US)-guided percutaneous radiofrequency ablation (RFA) for multiple breast fibroadenoma as an alternative to surgical resection. Sixty-five patients with multiple breast fibroadenoma accepted general anesthesia and US-guided percutaneous RFA in our hospital from September 2014 to January 2016. Contrast-enhanced US (CEUS) was used immediately after operation to determine whether the tumor was ablated completely. The complete ablation rate (CAR) and the change of focal volume were evaluated by CEUS at the 1st month and the 3rd month after operation. All the patients were diagnosed by needle biopsy. Among all the patients, 256 nodules were found. Forty-six nodules (17.96%) were located <5 mm from epidermis; 26 nodules (10.15%) were located below areola. Complete ablation was achieved for 251 nodules (98.04%) after the 1st month of operation. The volume reduce rate was 39.06% and 75.99% at the 1st and the 3rd month after operation, respectively, of which 45 nodules were completely absorbed (17.58%). There was a statistically significant difference of the volume reduction rate (VRR) after operation (P < 0.01) compared with preoperative breast nodules volume. There were no complications such as skin burn, hemorrhage, and hematoma, nipple discharge in the process during and after RFA. Given advantages of high CAR, mild injury, rapid recovery, and cosmetic outcome desired by the patients, RFA has the potential to become the preferred method in the treatment of breast fibroadenoma.