© 2022, The Author(s).Background: Circulating tumor cells represent an opportunity for the assessment of early recurrent disease or for real-time tracing of cancer. Glucose Regulated Protein 78 (GRP78) is known in the literature as a stress factor in endometrial cancer. We aimed to investigate the importance of the gene by targeting tumor traces circulating in the cell fluids of patients with Type 1 endometrial cancer, examining cell-free RNAs in patients’ samples and performing ROC analysis. Methodology: In this study, 32 endometrial cancer patients and 20 controls were included. This in vitro study evaluated, the GRP78 cell-free mRNA expression levels in endometrial cancer patients, by quantitative real-time polymerase chain reaction qRT–PCR Light Cycler. Receiver operating characteristic (ROC) analysis is a tool used to identify the precision of a diagnostic test or prediction model. In our study, we investigated whether the expression levels of cell-free GRP78 mRNA could be used as a diagnostic criterion. Results: The ROC curve results for endometrial cancer diagnostic criterion of cfRNA GRP78 mRNA indicated quite a significant value (p < 0.001). Conclusion: Current findings show that cell-free mRNA GRP78 is now a criterion that can be used together with smear mRNA GRP78 without the need for invasive methods in endometrial cancer studies.