Radioactive seed localization (RSL) is an advanced localization technique used for precise tumour excision in breast and axillary surgery, guided by the radioactivity of an implanted iodine-125 (125I) seed. Compared to conventional methods such as wire-guided localization (WGL) and radioactive occult lesion localization (ROLL), 125I-seeds in RSL offers several clear advantages: (1) point-source radioactivity enables precise tumour localization, improving complete excision rates and accuracy; (2) multiple seeds can be used to bracket the edges of extensive ductal carcinoma in situ (DCIS) or marking multifocal lesions; (3) the technique is suitable for both breast-conserving surgery and advanced axillary procedures such as MARI; (4) the long half-life of 125I-seeds permits implantation months in advance, facilitating use during neoadjuvant systemic therapy; (5) this also facilitates flexible scheduling; (6) studies confirm minimal radiation exposure to patients (including pregnant women and infants) and healthcare workers, when protocols are followed and seed activity is optimized. Initial challenges of introducing RSL include regulatory requirements regarding handling and the disposal of the seeds, requiring an extensive protocol, and administrative work. But successful clinical implementation demonstrates that these initial hurdles are outweighed by the sustained benefits in surgical accuracy, workflow efficiency, and patient satisfactory. In summary, RSL with 125I-seeds is a highly accurate, flexible, safe, and patient-centred method of tumour-localization, making it a valuable and increasingly indispensable tool in contemporary surgical management of breast cancer.