Backgroud <p>Accurate localization of nonpalpable breast lesions in breast-conserving surgery (BCS) is essential for achieving oncological radicality, preserving cosmetic outcomes, and reducing reinterventions for positive margins. Radioguided occult lesion localization (ROLL) and magnetic seed localization (MSL) are established alternatives to wire-guided methods, but comparative evidence remains limited.</p> Methods <p>This prospective, single-centre, randomized clinical trial evaluated the noninferiority of MSL compared with ROLL in achieving negative surgical margins, assessed surgical, organizational, and patient-reported outcomes, and included a costs analysis. A total of 260 women with nonpalpable breast lesions suitable for BCS were enrolled between June 2023 and July 2025 and randomized 1:1 to ROLL or MSL. The primary endpoint was margin negativity. Secondary endpoints included calculated resection ratio (CRR), operative time, complications, hospital stay, reoperation rate, and EQ-5D-5L patient-reported outcomes.</p> Results <p>Negative margins were achieved in 97.7% of ROLL and 93.1% of MSL cases (<i>p</i> = 0.14), confirming MSL noninferiority. Median CRR was identical (1.7, <i>p</i> = 0.61). Overall complication rates were comparable (6.2%-MSL vs. 4.7%-ROLL, <i>p</i> = 0.59), although postlocalization hematoma was more frequent with MSL (17% vs. 7%, <i>p</i> = 0.01). Hospital stay was significantly shorter with MSL (1 vs. 2 days, <i>p</i> = 0.001). Operative times were similar, and surgeon experience did not influence margin status, although attendings achieved lower CRR with ROLL. EQ-5D-5L scores were comparable except for “usual activities” dimension, which favoured ROLL.</p> Conclusions <p>MSL was noninferior to ROLL, with comparable safety and patient-reported outcomes. Magnetic seed localization was found to be costs-saving across all analysed subgroups. Our results show that MSL is an effective alternative for lesion localization in BCS.</p>