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We retrospectively investigated the clinical value of real-time ultrasonography (US)-magnetic resonance imaging (MRI) fusion imaging for second-look examination compared with conventional second-look US of 67 breast lesions in 55 patients with breast cancer. Real-time US-MRI fusion imaging significantly improved the preoperative detection of additional high-risk or malignant lesions in patients with breast cancer and can ultimately determine optimal treatment planning.This study was conducted to evaluate the clinical effect of real-time magnetic resonance imaging (MRI)-navigated ultrasonography (US) for preoperative second-look examination in patients with breast cancer.Between October 2013 and February 2015, 232 patients with breast cancer underwent MRI for staging; second-look US was performed in 70 patients to evaluate additional lesions suspected to be disease detected using MRI. We retrospectively included 67 lesions in 55 patients. Lesions were classified as detected on conventional US (group 1), and not visible on conventional US, but detected on MRI-navigated US (group 2). The imaging features between groups 1 and 2 were compared using Student t, χ2, or Fisher exact tests. We compared the detection rate and histopathology of additional lesions using a McNemar test.Heterogeneous background echotexture (69.6% [16 of 23] vs. 34.1% [14 of 41]) and lesion isoechogenicity (65.2% [15 of 23] vs. 7.3% [3 of 41]) on US and middle or posterior lesion depth on MRI (78.3% [18 of 23] vs. 46.3% [19 of 41]) were more common in group 2 (P < .05). More lesions were detected using MRI-navigated US (64 of 67; 95.5%) than conventional US (41 of 67; 61.2%; P < .01). Using MRI-navigated US we found more high-risk or malignant lesions than conventional US (21 vs. 11; P < .01). The optimal treatment plan was determined for 9 of 16 (56.3%) patients by virtue of MRI-navigated US.Real-time MRI-navigated US significantly improved the detection of additional high-risk or malignant lesions during second-look US in preoperative evaluation of patients with breast cancer and ultimately determined the optimal treatment plan.