Calretinin (CRT) is a calcium-binding protein that controls intracellular calcium signaling. Besides its prominent expression in neurons, serum CRT (sCRT) has recently been suggested as blood-based biomarker for pre-diagnostic mesothelioma detection. CRT is expressed in ovarian cancer tissues in up to 40% of cases; however, its clinical relevance as blood based-biomarker for ovarian cancer is unknown. sCRT was determined by calretinin enzyme-linked immunoabsorbent assay (Calretinin-ELISA, DLD Diagnostika GmbH) in a total of 515 serum samples from 116 healthy controls and 134 ovarian cancer patients (thereof 86% with FIGO III/IV), including samples at primary diagnosis and at four longitudinal follow-up time points in the course of treatment and at recurrence. sCRT level was significantly increased in ovarian cancer patients compared to healthy controls (ED=0.3ng/ml, P<0.001), was mostly independent from CA125 (r≤0.388) and enabled accurate discrimination between cases and controls (AUC=0.85). Higher sCRT level at primary diagnosis predicted suboptimal debulking (P<0.001) and was associated with advanced FIGO-stage (p<0.001) and increased volume of ascites (p<0.001). sCRT levels at primary diagnosis and its dynamics in the course of chemotherapy were independent predictors for poor PFS (HR=1.99, CI=[1.13-3.52], P=0.0181) and OS (HR=15.4, CI=[1.92-124], P=0.0099). Furthermore, sCRT at primary diagnosis or a relative sCRT increase in the time interval between surgery and the onset of chemotherapy were both independent predictors of platinum-resistance (OR=32.3, CI=[3.57-4282], P=0.000521; OR=2.41, CI=[1.37-6026], P=0.0271, respectively). This is the first study that suggests sCRT as liquid biopsy marker for independent prediction of platinum-resistance and prognosis. This article is protected by copyright. All rights reserved.