Purpose Readers need to be informed about potential pitfalls of 68 GaGa-PSMA-11 PET interpretation. Methods Here we report 68 GaGa-PSMA-11 PET findings discordant with the histopathology/composite reference standard in a recently published prospective trial on 635 patients with biochemically recurrent prostate cancer. Results Consensus reads were false positive in 20 regions of 17/217 (8%) patients with lesion validation. Majority of the false positive interpretations (13 of 20, 65%) occurred in the context of suspected prostate (bed) relapse (T) after radiotherapy ( n  = 11); other false positive findings were noted for prostate bed post prostatectomy (T, n  = 2), pelvic nodes (N, n  = 2), or extra pelvic lesions (M, n  = 5). Major sources of false positive findings were PSMA-expressing residual adenocarcinoma with marked post-radiotherapy treatment effect. False negative interpretation occurred in 8 regions of 6/79 (8%) patients with histopathology validation, including prostate (bed) ( n  = 5), pelvic nodes ( n  = 1), and extra pelvic lesions ( n  = 2). Lesions were missed mostly due to small metastases or adjacent bladder/urine uptake. Conclusion 68 GaGa-PSMA-11 PET at biochemical recurrence resulted in less than 10% false positive interpretations. Post-radiotherapy prostate uptake was a major source of 68 GaGa-PSMA-11 PET false positivity. In few cases, PET correctly detects residual PSMA expression post-radiotherapy, originating however from treated, benign tissue or potentially indolent tumor remnants. Trial registration number ClinicalTrials.gov Identifiers: NCT02940262 and NCT03353740.