Adjuvant radiotherapy and adjuvant endocrine therapy are commonly given to patients with invasive breast cancer or with ductal carcinoma in situ (DCIS). Although both therapies have been well established through a number of randomized studies, little is known about a possible interaction of both treatment modalities if they are given simultaneously. A number of in vitro studies have indicated that tamoxifen treatment might reduce the intrinsic radiosensitivity of MCF-7 breast cancer cells. Conversely, estradiol treatment increases the intrinsic radiosensitivity of MCF-7 cells. In one available animal study, an antagonistic effect of tamoxifen and ionizing radiation (XRT) could not be observed. Retrospective analyses of randomized clinical studies have not indicated an antagonistic effect of tamoxifen on the effectiveness of XRT, since local control has been consistently higher when XRT was combined with tamoxifen, compared with treatment with XRT alone, regardless of whether tamoxifen was started simultaneously with radiotherapy or after completion of radiotherapy. Currently there are no clinical data available that would suggest an adverse effect of adjuvant tamoxifen treatment started prior to or simultaneously with radiotherapy in breast cancer or DCIS. However, since an antagonistic effect of tamoxifen and simultaneous chemotherapy has been reported recently, the issue of simultaneous versus sequential radiation and tamoxifen treatment in breast cancer should be addressed in further studies.