Ovarian carcinomas are distinguished by their polyclonality, i.e., heterogeneity and polymorphism of their tissue. There is no marker available complying with the clinical demands in the case of ovarian carcinoma regarding satisfactory sensitivity and specificity. Therefore, we have simultaneously determined two entirely distinct tumor markers, serum ribonuclease activity (SRA) and cancer antigen 125 (CA 125), recommended in the literature with respect to ovarian carcinoma. After evaluation by logistic regression analysis, we found a specificity of 93% together with a sensitivity of 97% for the simultaneous determination of SRA and CA 125 (37 ovarian carcinomas, 11 cases without pathological findings after treatment, 11 benign tumors of the ovary, 61 controls). The patients are not exposed to increased stress by this simultaneous determination method compared to the determination of a single marker. The increased clinical validity justifies the recommendation of routine simultaneous determinations of SRA and CA 125 for diagnosis and monitoring of patients with ovarian carcinoma.