The presence of internal mammary (IM) lymph node metastases in breast cancer predicts outcome and may alter treatment. Standard imaging has limited usefulness for evaluation of the IM chain because of low sensitivity. Our preliminary studies suggested that [F-18]-2-fluoro-d-glucose positron emission tomography (FDG-PET) improves the detection of IM and mediastinal metastases. We therefore performed a retrospective review of women who underwent FDG-PET prior to treatment to determine the benefit of PET for imaging IM disease. The records of 28 consecutive patients undergoing FDG-PET prior to neoadjuvant chemotherapy for suspected locally advanced breast cancer (LABC) were reviewed. The presence of abnormal IM uptake on FDG-PET was noted. IM uptake on FDG PET was compared with standard radiographic imaging and was correlated with putative risk factors for IM involvement and with clinical patterns of failure. Patients did not undergo IM biopsy; however, patterns of failure were assessed to validate the FDG-PET findings. Clearly abnormal FDG uptake in the IM nodes was seen in 7 of 28 women (25%). Prospective conventional chest imaging failed to identify IM metastases in any patient. IM uptake on PET was associated with large size of the primary tumor (P = 0.03) and with inflammatory disease (P = 0.04). The presence of IM FDG uptake predicted failure by a pattern consistent with spread from IM lymph node metastasis. FDG-PET appears to be a useful noninvasive modality to detect IM metastases in LABC. Pathologic verification in a prospective study is necessary to confirm these findings.