Abstract Purpose Improved logistics and availability led to a rapid increase in the use of [¹⁸F]-PSMA-1007 for prostate cancer PET imaging. Initial data suggests increased uptake in benign lesions compared to [⁶⁸ Ga]-PSMA-11, and clinical observations found increased unspecific bone uptake (UBU). We therefore investigate the frequency and characteristics of UBU in [¹⁸F]-PSMA-1007 PET. Methods We retrospectively analyzed [¹⁸F]-PSMA-1007 PET scans from four centers for the presence of UBU, defined as a focal mild-to-moderate uptake (SUV_max < 10.0) not obviously related to a benign or malignant cause. If present, up to three leading UBUs were quantified (SUV_max), localized, and correlated to clinical parameters, such as age, PSA, injected dose, Gleason score, tumor size (T1–T4), and type of PET scanner (analog vs. digital). Additionally, clinical and imaging follow-up results and therapeutic impact were evaluated. Results UBUs were identified in 179 out of 348 patients (51.4%). The most frequent localizations were ribs (57.5%) and pelvis (24.8%). The frequency of UBUs was not associated with PSA, Gleason score, tumor size, age, or the injected [¹⁸F]-PSMA-1007 dose. UBUs were significantly more frequent in images obtained with digital PET/CT scans (n = 74, 82%) than analog PET/CT scans (n = 221, 40.3%) (p = .0001) but not in digital PET/MR (n = 53, 51%) (p = .1599). In 80 out of 179 patients (44.7%), the interpretation of UBUs was critical for therapeutic management and therefore considered clinically relevant. For 65 UBUs, follow-ups were available: three biopsies, three radiotherapies with PSA follow-up, and 59 cases with imaging. After follow-up, UBUs were still considered unclear in 28 of 65 patients (43%), benign in 28 (43%), and malignant in nine (14%) patients. Conclusion UBUs occur in two-thirds of patients imaged with [¹⁸F]-PSMA-1007 PET/CT and are significantly more frequent on digital PET scanners than analog scanners. UBUs should be interpreted carefully to avoid over-staging.