The purpose of this study was to evaluate the diagnostic accuracy of multiparametric evaluation of breast lesions combining information of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted imaging (DWI), and F-fluoro-deoxi-glucose (F-FDG) positron emission tomography/computed tomography (PET-CT). After approval of the institutional research ethics committee, 31 patients with suspicious breast lesions on MRI performed F-FDG PET-CT with a specific protocol for breast evaluation. Patients' mean age was 47.8 years (range, 29-77 years). Positron emission tomography and magnetic resonance imaging (PET-MRI) images were fused. A lesion was considered positive on multiparametric evaluation if at least 1 of the following was present: washout/type 3 kinetic curve on DCE-MRI, restricted diffusion on DWI with minimum apparent diffusion coefficient value <1.00 × 10 mm/s, and abnormal metabolism on F-FDG PET-CT (higher than the physiologic uptake of the normal breast parenchyma). Thirty-eight lesions with histologic correlation were evaluated on the 31 included patients, being 32 mass lesions (84.2%), and 6 nonmass lesions (15.8%). Lesions' mean diameter was 31.1 mm (range, 8-94 mm). Multiparametric evaluation provided 100% sensitivity, 55.5% specificity, 87.9% positive predictive value, 100% negative predictive value, and 89.5% accuracy, with 29 true-positives results, 5 true-negatives, 4 false-positives, and no false-negative results. Multiparametric evaluation with PET-MRI functional data showed good diagnostic accuracy to differentiate benign from malignant breast lesions, reducing the number of unnecessary biopsies, without missing any diagnosis of cancer in our case series.