BACKGROUND: Systemic inflammation has long been related with adverse survival outcomes in cancer patients, and its biomarkers, such as the Neutrophil-to-Lymphocyte Ratio (NLR), are recognized as poor prognostic indicators. However, the role of eosinophils in this field has been largely overlooked. Here, we describe two new pre-treatment biomarkers, expressed as Eosinophil-to-Lymphocytes Ratio (ELR) and Eosinophil*Neutrophil-to-Lymphocytes ratio (ENLR), and we analyse their impact on prognosis of endometrial cancer (EC) patients. METHODS: A total of 163 consecutive patients diagnosed with EC and treated with postoperative radiotherapy +/- chemotherapy in our institution from January 2011 to December 2015 were evaluated. The cohort was divided in two groups applying the cut-off value of 0.1 and 0.5 according to ROC curve for pre-treatment ELR and ENLR, respectively. After patients' stratification according to the ESMO-ESGO-ESTRO modified risk assessment, subgroup analyses were conducted. RESULTS: Higher values of ELR and ENLR were associated with worse OS (p = 0.004 and p = 0.010, respectively). On univariate analysis, the factors associated with shorter OS were ELR ≥ 0.1 (HR = 2.9, p = 0.017), ENLR ≥ 0.5 (HR = 3.0, p = 0.015), advanced FIGO stage (HR = 3.4, p = 0.007), endometrioid histology (HR = 0.26, p = 0.003) and ESMO-ESGO-ESTRO high-risk (HR = 10.2, p = 0.023). On multivariate Cox regression, higher ELR and ENLR were independently associated with a worse outcome adjusted for the standardly applied prognostic factors. CONCLUSIONS: Increased values of ELR and ENLR portend worse OS in EC, especially in patients classified by the ESMO-ESGO-ESTRO guidelines as a high-risk group. To our best knowledge, this is the first report describing eosinophils-related ratios as prognostic biomarkers in malignant tumours.