Ovarian cancer is the most overrepresented malignancy diagnosed in women with dermatomyositis. Unfortunately, screening with pelvic examination rarely detects this cancer prior to the development of metastatic disease. Our objective was to examine the use of serum CA-125 antigen levels in screening patients with dermatomyositis for ovarian cancer. A single blinded, case-control study was conducted in our institution of CA-125 levels in 14 women diagnosed with dermatomyositis between 1986 and 1993, 4 of whom subsequently developed ovarian cancer. In the 4 patients who developed ovarian cancer ("cases"), CA-125 determinations were performed on serum stored 5 to 19 months prior to the diagnosis of ovarian cancer. In the remaining 10 patients ("controls"), serum was drawn for CA-125 level determination at the time of the study, and simultaneous gynecologic and endovaginal ultrasound examinations were performed to exclude clinical evidence of ovarian cancer. All CA-125 serum measurements were performed simultaneously by a technician blinded to disease status using one diagnostic kit. CA-125 was found to be elevated in 2 patients with ovarian cancer (on serum obtained 5 and 13 months prior to the date of diagnosis of ovarian cancer) and in none of the control patients without clinical or ultrasound evidence of ovarian cancer (relative risk = 20, 95% confidence interval = [0.64, 666]). In these 14 patients, the sensitivity of CA-125 elevation for detection of ovarian cancer was 50%, and specificity was 100%. Serum CA-125 screening for ovarian cancer in patients having dermatomyositis may be useful; however, prospective studies are needed to confirm this and to determine the effect of screening on cancer stage at diagnosis and long-term survival.