The objective of this study was to test the reliability and validity of the Iranian version of the European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR23). The English-language version of the questionnaire was translated into Persian (Iranian language) and its final form was approved by the EORTC Study Group on Quality of Life and then it was used in this study. The questionnaire was administered at two points in time to a consecutive sample of 168 newly diagnosed breast cancer patients and almost all of them (99%) found the questions easy to understand and acceptable. Cronbach's alpha coefficient for multi-item scales (to test reliability) ranged from 0.63 to 0.95 at baseline and from 0.75 to 0.92 at follow-up administration of the questionnaire. Validity analysis was performed using known-groups' comparison analysis. The results showed that all functional and symptom scales discriminated between sub-groups of patients differing in clinical status as defined by their performance status and disease stage. In addition, all functional and symptoms scales detected change over time, as a function of changes in patients' performance status. In general, the findings of this study indicated that the Iranian version of the EORTC QLQ-BR23 is a reliable and valid supplementary measure of the quality of life in breast cancer patients and can be used in clinical trials and studies of outcome research in oncology.