Purpose To deliver patient-reported outcome (PRO) reference data for breast cancer and various other breast diseases to facilitate the interpretation of PRO scores during routine breast cancer treatment. Methods To determine reference baseline values for the PRO measures EORTC QLQ-C30 and EORTC QLQ-BR23, PRO data captured in the breast cancer centre at Charité – Universitätsmedizin Berlin from 2016 to 2021 were evaluated. As part of the clinical routine, ambulatory patients were asked to answer a digital survey regarding their medical history, current health status and health-related quality of life using the aforementioned questionnaires prior to their doctor’s appointment in the outpatient breast clinic. Adjusted linear and variable dispersion beta regression models were used to compare different diagnosis groups. Results A total of 3689 patients were included in the digital PRO program, of which 1478 were eligible for this study; 729 had invasive breast cancer or ductal carcinoma in situ, 270 patients were diagnosed with fibroadenoma and 479 patients had other breast diseases such as cysts, mastopathy or abscesses. Overall, patients with breast cancer reported worse scores in almost all domains except for role functioning, sexual functioning and body image. Compared to previously published reference scores for early breast cancer, the current data show a more pronounced impact on perceived emotional and cognitive functioning. Conclusion The results of this study are of high value for the interpretation of PROs and facilitate their use in clinical practice and clinical trials. The scores indicate an urgent need for psychosocial support prior to treatment.