The purposes of this study were to evaluate the diagnostic performance of dedicated breast PET (dbPET) in cases of unexpected uptake and to define parameters associated with malignancy. There are two types of high-resolution dbPET systems. One has two platelike detectors that compress the breast. This study was conducted with the other type, on which the patient lies prone and the breast hangs through a ring without compression. In total, 627 consecutively registered women underwent 18F-FDG PET/CT and dbPET for pretherapeutic or posttherapeutic evaluation of breast cancer, prior suspicion of breast cancer, or cancer screening. Areas of abnormal FDG uptake, excluding known breast cancers, were analyzed. Uptake was morphologically categorized as focus, mass, or non-mass. Quantitative values were obtained, including the maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), total lesion glycolysis (TLG), metabolic tumor volume (MTV), and lesion-to-background ratio (LBR). Clinical parameters were also assessed. Parameters were compared between breast cancer and noncancer groups; multivariate logistic regression analysis was performed. Of 40 instances of abnormal uptake, 13 were breast cancer. Morphologic features differed between cancer and noncancer groups (p = 0.0122). Among the cancers, 76.9% (10/13) had mass, 15.4% (2/13) had nonmass, and 7.7% (1/13) had focus uptake. Of noncancerous findings, 3.7% (1/27) were mass, 40.7% (11/27) nonmass, and 55.6% (15/27) focus uptake. SUVpeak (p = 0.0234), TLG (p = 0.0017), MTV (p = 0.004), and LBR (p = 0.0432) also differed between groups. Results of multivariate analysis indicated that morphologic category at dbPET was independently associated with malignancy. Morphologic features of abnormal uptake at dbPET are associated with breast cancer and may be useful for diagnosing lesions of unknown histologic composition.