Abstract [Background] Preoperative breast MRI is used to evaluate for additional and extent disease for newly diagnosed breast cancer patients with dense breasts. The potential benefit of preoperative MRI is still being controversial. However, when breast conserving surgery (BCS) is considered for non-mass enhancement (NME) on MRI, the precise image-guided localization is required. Although breast ultrasound (US) plays an adjunctive role in evaluation of MRI findings in preoperative planning for BCS, NME is less likely than a mass or focus to have a US correlate. Furthermore, the presence of NME increases the re-operation rate in BCS because of the difficulty in evaluating the tumor margin. An MRI/US fusion imaging has recently been developed that uses either real-time virtual sonography TM (RVS) or volume navigation TM (Vnav), and can overlay an US with the MRI image of the same site in real time by using magnetic position tracking system. The purpose of this prospective multicenter study was to evaluate the effect of MRI/US fusion imaging for preoperative planning using non-wire localization technique in BCS in patients with NME. [Methods] In 3 Japanese hospital, 13 patients who had lesions with NME that exceeded the US hypoechoic area were enrolled in this study from 2019 to 2022. Written informed consent was acquired, and then an additional supine MRI using a body surface coil was performed. During preoperative planning before BCS, RVS/Vnav was used to determine the NME enhancing area and to mark the area on the skin. Tissue markers were inserted under US at a location assessed by RVS/Vnav as the edge of extent of NME. We analyzed both the surgical margin positivity rate and the reoperation rate. [Results] The preoperative diagnosis by core needle biopsy were 6 DCIS and 7 invasive ductal carcinoma. NME distribution types were 7 segmental, 3 focal, 2 linear 4 and 1 regional. The median diameters of the NME and hypo-echoic lesions were 31 mm (range: 18–39 mm) and 16 mm (range: 9–32 mm), respectively (p = 0.0005). After confirming the localization of the tissue marker with intraoperative US, 12 lumpectomy and 1 quadrantectomy were conducted. The median specimen weight was 63g (range: 54-105g). In the final pathologic diagnosis of excised specimens were 5 DCIS and 8 IDC. In 8 cases (62%), the pathologic diameter was larger than the US diameter. All surgical margins were negative. None of the patients required additional resection. [Conclusions] The findings of study suggest that preoperative planning using non-wire localization technique under MRI/US fusion imaging for BCS in patients with NME could improve both a surgical margin positive rate and a reoperation rate. Citation Format: Shogo Nakano, Manabu Futamura, Keitaro Kamei, Takayoshi Uematsu, Miwa Yoshida, Sadako Akashi-Tanaka, Junta Sakakibara, Ichiro Isomoto, Hiroko Satake, Maiko Takahashi, Minami Hatono, Junko Araki. Impact of an MRI/US fusion imaging for preoperative planning using non-wire localization technique in breast conserving surgery in patients with non-mass enhancement on MRI. A prospective multicenter study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-07-08.