Purpose: We evaluated the incidence and malignant risk of focal breast lesions incidentally detected by 18F-FDG PET/CT. Various PET/CT findings of the breast lesions were also analyzed to improve the differentiation between benign from malignant focal breast lesions. Materials & Methods: The subjects were 3,768 consecutive 18F-FDG PET/CT exams performed in adult females without a history of breast cancer. A focal breast lesion was defined as a focal 18F-FDG uptake or a focal nodular lesion on CT image irrespective of 18F-FDG uptake in the breasts. The maximum SUV and CT pattern of focal breast lesions were evaluated, and were compared with final diagnosis. Results: The incidence of focal breast lesions on PET/CT in adult female subjects was 1.4% (58 lesions in 53 subjects). In finally confirmed 53 lesions of 48 subjects, 11 lesions of 8 subjects (20.8%) were proven to be malignant. When the PET/CT patterns suggesting benignancy (maximum attenuation value > 75 HU or < 30 HU; standard deviation of mean attenuation > 20) were added as diagnostic criteria of PET/CT to differentiate benign from malignant breast lesions along with maximum SUV, the area under ROC curve of PET/CT was significantly increased compared with maximum SUV alone (0.680¡¾0.093 vs. 0.786¡¾0.076, p<0.05). Conclusion: The malignant risk of focal breast lesions incidentally found on 18F-FDG PET/CT is not low, deserving further diagnostic confirmation. Image interpretation considering both 18F-FDG uptake and PET/CT pattern may be helpful to improve the differentiation from malignant and benign focal breast lesion. (Nucl Med Mol Imaging 2008;42(6):456-463)