Abstract Introduction Breast magnetic resonance imaging (MRI) is performed for preoperative screening of breast cancer and surveillance of BRCA gene carriers, and some lesions, called MRI-detected lesions, can only be detected by MRI. When MRI-detected lesions are found, second-look ultrasound (US) is recommended as the first choice for confirmation. However, the detection of MRI-detected lesions by conventional B-mode (cB-mode) second-look US varies from institution to institution, and it is often difficult to ensure objectivity and reproducibility. We use an MRI/US fusion technique called real-time virtual sonography (RVS) for the detection of MRI-detected lesions. RVS uses a magnetic position tracking system to display real-time US images on the same monitor as MRI images. Few reports on second-look US using RVS have examined its detection rate of MRI-detected lesions and the histopathological results of these lesions. In this study, we retrospectively reviewed MRI-detected lesions identified by second-look US using RVS but not by cB-mode second-look US from January 2018 to December 2022, with the goal of evaluating these lesions’ pathological characteristics. Materials and methods Consecutive patients who had one or more MRI-detected lesions not detected by cB-mode second-look US were enrolled in this study between January 2018 and December 2021. Second-look US using RVS was conducted after an additional supine MRI with a body surface coil was performed. Results A total of 36 patients with 38 lesions were included in this study. The mean age was 54 years old (range: 31–76). We were able to detect 31 (82%) of the 39 MRI-detected lesions by second-look US using RVS. These lesions were characterized as follows: mass, 14; non-mass-enhancement (NME), 13; and focal, 4. US-guided biopsy or excisional biopsy was performed on all lesions, and 11 (35%) of 31 lesions were malignant. We were able to detect 14 (74%) of the 19 mass lesions, and 3 were malignant (invasive ductal carcinoma (IDC) [luminal A type] in all 3 cases). We detected 13 (93%) of the 14 NME lesions, and 7 were malignant: 6 were ductal carcinoma in situ (DCIS) (high grade, 3; intermediate grade, 2; and low grade, 1), and 1 was IDC (luminal A type). Finally, we were able to detect 4 (80%) of the 5 focal lesions, 1 of which was malignant (DCIS [low grade]). Of 22 patients aged 55 years or younger, 3 had malignant lesions (IDC [luminal A type] in 2, DCIS [high grade] in 1). Of 15 patients aged 56 years or older, 8 had malignant lesions (DCIS in 7 [high grade, 2; intermediate grade, 2; low grade, 1] and IDC [luminal A type] in 1). Conclusions In this study, second-look US using RVS identified 82% of MRI-detected lesions that were not identified with cB-mode second-look US. Of these MRI-detected lesions, 35% were malignant. These results suggest that second-look US using RVS is useful for identifying MRI-detected lesions that are not detected by cB-mode second-look US. Citation Format: Masayuki Saito, Hirona Banno, Yukie Ito, Mirai Ido, Manami Goto, Takahito Ando, Yukako Mouri, Junko Kousaka, Kmihito Fujii, Tsuneo Imai, Shogo Nakano. The efficacy of an MRI/US fusion technique for MRI-detected lesions previously undetected by conventional B-mode second-look US [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 PO2-07-08.