The purpose of this study is to report further about the statistically significant results from a prospective study, which suggests that fusion of prone F-18 Fluoro-deoxy-glucose (FDG) positron emission tomography (PET) and magnetic resonance (MR) breast scans increases the positive predictive value (PPV) and specificity for patients in whom the MR outcome alone would be nonspecific. Thirty-six women (mean age, 43 years; range, 24-65 years) with 90 lesions detected on MR consented to undergo a FDG-PET scan. Two blinded readers evaluated the MR and the computer tomography (CT) attenuation-corrected prone FDG-PET scans side-by-side, then after the volumes were superimposed (fused). A semiautomatic, landmark-based program was used to perform nonrigid fusion. Pathology and radiologic follow-up were used as the reference standard. The sensitivity, specificity, PPV, negative predictive value (NPV), and accuracy (with 95% confidence intervals) for MR alone, FDG-PET alone, and fused MR and FDG-PET were calculated. The median lesion size measured from the MR was 2.5 cm (range, 0.5-10 cm). Histologically, 56 lesions were malignant, and 15 were benign. Nineteen lesions were benign after 20-47 months of clinical and radiologic surveillance. The sensitivity of MR alone was 95%, FDG-PET alone was 57%, and fusion was 83%. The increase in PPV from 77% in MR alone to 98% when fused and the increase in specificity from 53% to 97% were statistically significant (p < 0.05). The false-negative rate on FDG-PET alone was 26.7%, and after fusion this number was reduced to 9%. FDG-PET and MR fusions were helpful in selecting which lesion to biopsy, especially in women with multiple suspicious MR breast lesions.