Ovarian cancer is responsible for the highest fatality rate among the gynecologic malignancies, and there is a great urgency in defining screening tests for its early detection. Presently, CA125 is the only serum marker recommended for early detection (in combination with transvaginal ultrasonography) in hereditary syndromes and for differential diagnosis in suspicious pelvic mass. However, given the complexity of the pathogenesis and of the tumor-host interaction, it is unlikely that a single serum biomarker bears sufficient information for the specific discrimination of ovarian cancer at its very early stage form other non-malignant pelvic lesions. Consistently, CA125 has demonstrated its utility for monitoring the therapy and prognosis, but owing to its scarce sensitivity and specificity it is not recommended for screening of ovarian cancer in asymptomatic patients. Recently, the introduction of high-throughput multiplex technologies, that allow to measure simultaneously a large number of molecules in the femtomolar range of concentration in the serum, has led to the definition of panels of biomarkers for the early detection of ovarian cancer. Here, we review the latest patents in this field.