The aim of the present study was to evaluate the psychometric properties of the measure among a sample of Iranian patients with bone metastases. One hundred and seventy-seven patients with bone metastases undergoing various treatments were recruited from Imam Khomeini Hospital in Tehran to participate in the study. The coefficient alpha affirmed internal consistency reliability of the Quality of Life Questionnaire for patients with Bone Metastases (QLQ-BM22). This measure discriminated well between subgroups of the patients based on performance status and responding to treatment. Confirmatory factor analysis confirmed the factorial validity of the four hypothesized QLQ-BM22 scales. Patients in this study had a similar interpretation of the items on the QLQ-BM22 regardless of gender. All scales of the QLQ-BM22 were sensitive to change after treatment over a month's follow-up, with the exception of psychosocial aspects. The Persian version of the EORTC QLQ-BM22 was highly reliable and is valid for use among patients with bone metastases who are undergoing various treatment regimes.