A large number of breast cancer patients receiving adjuvant chemotherapy is suffering from fatigue. Until now there has been a lack of knowledge concerning the course of fatigue in breast cancer patients between two cycles of adjuvant chemotherapy. Therefore a prospective cohort study was conducted including 151 breast cancer patients from six hospitals in The Netherlands. The object of the study was to investigate the course of fatigue between the third and the fourth cycles of adjuvant chemotherapy, and to prove whether that course is influenced by different chemotherapy schedules. The patients were treated either with a doxorubicin containing schedule (21 or 28 days) or with a combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF, 28 days). To assess fatigue patients were asked to write a diary cotaining the Shortened Fatigue Questionnaire (SFQ) from the beginning of the third cycle to the start of the fourth one. All days after completion of the third chemotherapy treatment were analysed. The main hypothesis to be tested was that the maximum fatigue level occurs in the first four days after treatment. Results revealed a chaotic pattern of fatigue between both cycles of chemotherapy in each of the treatment group. Smooth (splines) curves showed an average highest level of fatigue on day 3 post treatment. For the regimens with 28-days-intervalls another peak of fatigue was registered on day 11. A significant larger number of patients experienced maximum fatigue levels before day 5. The course of fatigue in the CMF group was significantly different compared with both doxorubicin groups. Women of the CMF group experienced lower fatigue peaks than patients of other groups. The results confirm the main hypothesis. The first days after treatment with chemotherapy are the worst ones for breast cancer patients. The course of fatigue is significantly related to the type of chemotherapy. Knowing these effects patients can better prepare oneself and their daily living for the time of adjuvant chemotherapy.