The use of radioactive seed localization (RSL) as an alternative to wire localizations (WL) for nonpalpable breast lesions is rapidly gaining acceptance because of its advantages for both the patient and the surgical staff. This paper examines the initial experience with over 1,200 patients seen at a comprehensive cancer center. Radiation safety procedures for radiology, surgery, and pathology were implemented, and radioactive material inventory control was maintained using an intranet-based program. Surgical probes allowed for discrimination between 125I seed photon energies from 99mTc administered for sentinel node testing. A total of 1,127 patients (median age of 57.2 y) underwent RSL procedures with 1,223 seeds implanted. Implanted seed depth ranged from 10.3-107.8 mm. The median length of time from RSL implant to surgical excision was 2 d. The median 125I activity at time of implant was 3.1 MBq (1.9 to 4.6). The median dose rate from patients with a single seed was 9.5 µSv h-1 and 0.5 µSv h-1 at contact and 1 m, respectively. The maximum contact dose rate was 187 µSv h-1 from a superficially placed seed. RSL performed greater than 1 d before surgery is a viable alternative to WL, allowing flexibility in scheduling, minimizing day of surgery procedures, and improving workflow in breast imaging and surgery. RSL has been shown to be a safe and effective procedure for preoperative localization under mammographic and ultrasound guidance, which can be managed with the use of customized radiation protection controls.