BACKGROUND: Tamoxifen (TAM) is well established in the adjuvant therapy of breast cancer. However, the timing of TAM therapy, concurrent or after radiotherapy, is controversial. METHOD: Literature is reviewed with respect to experimental and clinical data on interaction of TAM and radiation on tumor control and radiation side effects. RESULTS: In vitro data support the concept of antagonistic effects of concurrent TAM and radiation on tumor cells, but in animal models a synergistic effect was seen. Considering the modulation of TAM effects by estrogen and growth factor receptors, two-dimensional systems may not be suitable for studying the interaction of TAM and radiation. From a clinical perspective, a tumor-protective effect of TAM therapy concurrent with radiation was not evident. However, prospective studies addressing this question adequately are not available at the time. CONCLUSION: Although some studies indicate an enhancement of lung and subcutaneous fibrosis after TAM therapy, the side effects are mild and at this point do not seem to warrant withholding TAM.