The Center for Epidemiological Studies Depression Scale (CES-D) is commonly used to measure depressive symptomatology in cancer patients, yet there is little known about the psychometric properties of the measure when applied to a cancer population. The aim of this study was to examine the psychometric properties of the CES-D with cancer patients. For purposes of comparison, the psychometric properties of the CES-D were assessed both in women undergoing treatment for breast cancer and women with no history of cancer. The CES-D and other study measures were administered to women undergoing treatment for breast cancer on two occasions: prior to treatment and midway through treatment. The measures were also administered to a group of women similar in age to the cancer patients who had no history of any type of cancer. These healthy comparison subjects were also assessed on two separate occasions. The CES-D was found to have good internal consistency, with alpha coefficients > 0.85 for both groups, as well as adequate test-retest reliability in both groups. Construct validity was demonstrated in two ways, via comparisons between the groups and by comparing the CES-D with measures of fatigue, anxiety, and global mental health functioning. The CES-D was established as a valid and reliable measure of depressive symptomatology in this sample of breast cancer patients. This measure may be appropriate for use in clinical psychosocial research with cancer patients, yet further research is needed to evaluate its usefulness in other cancer populations. The importance of measuring psychological symptoms with standard measures that have been validated with cancer patients is highlighted.