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) Quality of Life Questionnaire (QLQ-C30). 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 before it was used in this study. The questionnaire was administered at two time points 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. Crohnbach's alpha coefficient for multi-item scales (to test reliability) ranged from 0.48 to 0.95 at baseline and from 0.52 to 0.98 at follow-up administration of the questionnaire. Validity was checked using two methods: inter-scale correlation and known-groups comparison. Almost all inter-scale correlations were statistically significant in the expected direction. Known-groups comparison analysis showed that all functioning and symptom scales discriminated between subgroups of patients differing in clinical status as defined by their performance status and disease stage. In general, the findings of this study indicate that the Iranian version of the EORTC QLQ-C30 is a reliable and valid measure of quality of life in cancer patients and can be used in clinical trials and studies of outcome research in oncology.