The objective of this feasibility study was to identify suitable surrogate parameters for a randomized confirmative trial with mistletoe treatment in patients with breast cancer. Tolerability,quality of life, hematological and immunological parameters were evaluated during postoperative chemotherapy. This prospective open 2-armed non-randomized study compared 33 patients with primary breast cancer during adjuvant chemotherapy (CMF or EC) and simultaneous treatment with Iscador M 5 mg spezial (IM spez) with 33 controls without mistletoe. Before and 14 days after chemotherapy hematology, lymphocyte subpopulations, stimulability of lymphozytes and quality of life(EORTC QLQ-C30, BR23) were assessed. Although there was a slight increase in thrombocytes within normal values (p =0.01), no clinically important laboratory parameter was favorable in the mistletoe group during the trial. There was no difference in immuno suppression due to chemotherapy. We found a lower frequency of nausea/vomiting and systemic therapy side effects (EORTC)during add-on-therapy with mistletoe (p = 0.02 each). Glucocorticoidco treatment in the mistletoe group was less frequent (p = 0.006), as well. In general, the add-on-therapy was well tolerated, taking into account that dose reduction was often necessary at the beginning of the chemotherapy because of large local reactions at the site of the injections. Therefore, blinding seems impossible if treatment with mistletoe and chemotherapy is started more or less simultaneously. Reductions in quality of life seem to be smaller during add-on-therapy with mistletoe. Laboratory parameters showed no difference compared to the control group. Quality of life and reduction of glucocorticoid cotreatment should be further evaluated.