Objective To prospectively evaluate the breast cancer detection of prone breast positron emission tomography (PET) images in comparison with supine whole-body PET images. Material and methods One hundred and eighteen female patients (age range 28-91 years) with 122 lesions suspected of having breast cancer underwent fluorine-18 fluorodeoxyglucose PET for preoperative staging. After the whole-body image was acquired, prone breast PET imaging was performed. The findings from both images were compared with the histopathologic results. Sensitivity, specificity, positive predictive value, negative predictive value (NPV), and accuracy were used to compare the diagnostic accuracy of prone breast PET images with that of whole-body PET images. Results Sensitivity, specificity, positive predictive value, NPV, and accuracy of whole-body PET images were 83, 50, 97, 17, and 80%, and of prone breast PET images they were 95, 50, 96, 43, and 93%. Ten of 114 breast cancerous lesions (8.8%) were detected on prone breast PET images alone. Statistical difference was found between the sensitivity, accuracy, and NPV of prone breast PET images and those of whole-body PET images (P < 0.0001 for sensitivity and accuracy and P < 0.0009 for NPV). Conclusion Our data about the 122 lesions, suspected of breast cancer, with regard to the usefulness of prone breast PET imaging indicate that prone breast PET images are effective in detecting breast cancer.