This study evaluates compliance and persistence in adjuvant endocrine breast cancer (BC) therapy by clearly analyzing reasons of therapy cessation by differentiating clinical meaningful situations. In order to illuminate the complex field of personal motivation to therapy, a single institution study with a more individual-based approach might better be suited to provide a detailed case documentation than the more epidemiologic approach of large database studies. An unselected cohort of 698 patients (≤ 80 years) diagnosed with hormonal receptor-positive BC from 1997 to 2008 at the University Hospital Basel, Switzerland, was analyzed. The term "non-persistence" was exclusively used for patients where the discontinuation of endocrine therapy (ET) could have been modified by more intensive care and improved counseling (e.g., in women who lost faith/motivation to therapy or those who suffered from therapy-related side effects). These cases must be differentiated from cases where therapy cessation was inevitable (e.g., due to recurrent disease or severe intercurrent illness). Out of the 685 patients to whom ET was recommended, 42 patients (6.1%) refused and never began treatment (non-compliance). Women younger than 50 were more likely to be non-compliant (P < 0.001). 12.9% of the patients who started therapy were non-persistent to therapy. Patients who were treated by general practitioners tended to be non-persistent more often compared to those treated by oncologists (17.7% vs. 11.3%; P = 0.07). The aim of a non-persistence rate between 10 and 15% is realistic when patients are treated by specialized oncologists. Interventions are needed to support patients, particularly the younger ones, to comply with therapy. Efforts should be made to make sure that all physicians, above all general practitioners, who are involved in BC treatment, are provided with current knowledge as to guarantee an optimal patient management.