A 71-year-old woman presented with a 6-month history of a noticeable masses in the left breast. “Orange peel” skin was observed on the left breast (a). Biopsy of the breast masses and axillary lymph nodes (LNs) revealed invasive ductal carcinoma of the breast. Immunohistochemistry was positive for HER2 (3 +), but negative for ER and PR. PET/CT was performed for tumor staging, and the patient was enrolled in the prospective trial on the comparison of [18F]FDG and 68Ga-labeled fibroblast-activated protein inhibitor-04 ([68Ga]Ga-FAPI-04) PET/CT in various cancers. This study was approved by the institutional review board and was registered at clinical-trials.gov (NCT04416165). Written informed consent was obtained from this patient. [18F]FDG PET/CT showed mild radiotracer uptake in the left breast masses (solid arrow, SUVmax 4.3) and enlarged axillary LNs (dotted arrows) (b). [68Ga]Ga-FAPI-04 PET/CT was performed 2 days after [18F]FDG PET/CT. Intense [68 Ga]Ga-FAPI-04 uptake was observed in the left breast masses (solid arrow, SUVmax = 48.9) and axillary LNs (dotted arrows). Surprisingly, [68Ga]Ga-FAPI-04 PET/CT showed numerous foci of intense activity in the skeleton (arrowheads, SUVmax = 34.9), suggesting bone metastases (c). However, the bone lesions showed no abnormal uptake on [18F]FDG PET and no morphological changes on CT (d). PET/CT-guided biopsy was performed in the FAPI-avid bone lesions (right ilium) (e). Histopathology revealed metastatic breast cancer with positive HER-2 expression (f–g).