Endometrial cancer is the most common pelvic genital cancer in women. Its incidence is increasing. Unlike the successful screening method for cervical cancer, there is no such equivalent procedure for the early diagnosis of endometrial cancer. Screening procedures currently being tested are too insensitive and nonspecific while diagnostics are either too complex or invasive. In Austria, a multicenter study was begun to search for parameters appropriate for a screening program. 138 women were selected based on anamnestic, serologic and cytologic risk factors. 68 women were diagnosed with endometrial cancer, 70 patients had abnormal bleeding. There were no significant differences in age and menopausal status. Secondary diseases including diabetes mellitus, hypertonia and adipositas were evenly distributed in both groups. In addition to the routine hormone analyses, we tested the patients' plasma for differences in melatonin levels. We found a significant correlation (p < 0.001) between melatonin plasma levels and the presence of endometrial cancer. The mean plasma melatonin value was 6.1 pg/ml in the cancer-positive group and 33.2 pg/ml in the cancer-negative control group resulting in a 6-fold difference between the two groups. We conclude that decreasing melatonin plasma levels may be an indicator of endometrial cancer and that this may therefore be used as a reliable screening parameter.