Objective: To explore the expression level and prognostic significance of erythropoietin receptor (EPOR) in patients with breast cancer (BRCA) based on estrogen receptor (ER) status and different molecular subtypes. Methods: The Cancer Genome Atlas (TCGA) and GTEx data were collected in GEPIA initially to identify the dysregulated genes. Further, bc-GenExMiner 4.1 online bioinformatics tool was used to evaluate EPOR mRNA differential expression level according to different classification of clinicopathologic parameters in patients with breast cancer. Additionally, the prognostic value between EPOR mRNA expression and free survival of metastatic relapse (MR) or any event (AE, namely any relapse or death) in patients with breast cancer was done. Results: EPOR mRNA was significantly downregulated in BRCA (1 085 cases) compared to normal tissues (291 cases) (P<0.05). Univariate Cox analysis revealed that high EPOR mRNA expression was remarkably correlated to a decreased risk of MR (HR: 0.79, P<0.000 1) and AE (HR: 0.87, P=0.000 7) especially in breast cancer patients with ER+. Besides, high EPOR mRNA level also associated with a favorable MR-free survival (HR: 0.81, P=0.007 2) and AE-free survival (HR: 0.88, P =0.029 9) in ER+breast cancer patients. However, no similar above phenomenon was detected in ER- patients. Moreover, the subsequent prognostic adjusted analyses and univariate Cox analysis of AE based on SSP or SCM molecular subtypes validated the above results. Conclusion: EPOR mRNA level is a valuable prognostic indicator for patients with ER+ breast cancer.