A variety of health status questionnaires have been used in physical rehabilitation studies involving women with breast cancer, but the usefulness of these questionnaires as measures of physical, mental, and social well-being has not been firmly established in this population. This study was conducted to assess the convergent and discriminative properties of the RAND 36-Item Health Survey and the Functional Living Index-Cancer (FLIC). Both questionnaires were administered concurrently to 110 outpatients treated surgically for breast cancer at a National Cancer Institute-designated Comprehensive Cancer Center. Bivariate correlations and a multi-trait-multi-method matrix were used to evaluate convergent validity between summary and subscale scores from both questionnaires. Discriminative validity was assessed by testing for expected differences between women who were treated for breast cancer with and without secondary lymphedema. Correlations between overall quality-of-life scores produced by both questionnaires were modest, indicating that the instruments focus on somewhat different aspects of health-related quality of life. Global quality-of-life and physical well-being scores were lower among women with lymphedema secondary to breast cancer. The FLIC demonstrated greater sensitivity to group differences in emotional well-being. The results suggest that neither questionnaire can be replaced by the other in studies of women treated for breast cancer. Both questionnaires were able to distinguish physical functioning deficits in women with lymphedema secondary to breast cancer, but symptom- or treatment-specific measures may be required to assess more subtle difficulties related to the emotional aspects of health and functioning in this population.