Ovarian cancer is not common, but it is still the fifth leading cause of death from malignant diseases among women worldwide. More than 200,000 women are diagnosed with ovarian cancer each year globally. Due to its asymptomatic course, most patients are diagnosed at a late stage. Therefore, ovarian cancer (OC) has the highest mortality among gynecological malignancies. Unfortunately, there is no adequate screening program for the early detection of ovarian cancer, and as a result, this diagnosis escapes clinicians. The protocol for early diagnosis of OC is currently a combination of elevated cancer antigen 125 (CA 125) and transvaginal ultrasonography (TVUS). However, it does not meet the necessary cost-effectiveness criteria and is therefore not recommended by any working group to screen ovarian cancer in the general population. The biomarkers with the highest informative value should be selected individually or combined in multi-biomarker panels from the many biomarkers strongly associated with OC. Numerous such panels of biomarkers and algorithms have been developed for the early diagnosis and differentiation of OC from other benign ovarian diseases. These panels or biomarkers need to be sufficiently reliable and show measurable changes in non-invasive samples obtained from patients with early-stage OC. Their reliability would significantly reduce mortality from this aggressive disease and improve the patient’s prognosis.