Background: Studies have shown that Enhancer-of-zeste homologue 2 (EZH2) plays an important role in carcinogenesis in the breast cancer, and invasion and progression of the disease. We aimed to assess the prognostic value of different molecular subtypes of breast cancer in relation to EZH2 expression. Methods: We performed a cross-sectional analytical research study on 100 breast cancer women. Survival analysis was then performed using the Kaplan–Meier method, with log-rank tests to assess statistical significance between groups. To assess the effects of variables on OS and DFS, a Cox proportional-hazard model was then used to give adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Samples were collected for 100 women with breast cancers, with follow-up data collected over a 5-year period. The mean age was 51.5 ± 9.54 years (range, 34–75 years), By molecular subgroup, 43% had luminal A tumors, 41% had luminal B tumors, 9% had HER2 tumors, and 7% had TNBC tumors. Overall, 74% had high EZH2 expression, which was most common for the luminal A subtype (43.2%) and least common for the TNBC subtype (8.1%). There was no significant correlation between subgroups by EZH2 expression (P = 0.33). Conclusions: In conclusion, although our results provide some interesting insights, there remains controversy about the prognostic value of different molecular subtypes of breast cancer in relation to EZH2 expression. Given that there are very few studies on this topic, we advocate further research with larger sample sizes and the inclusion of molecular techniques. Editorial acknowledgement: This study was conducted as part of a fellowship thesis for Dr Boostani (thesis no 94/5-9/30). Dr Robert Sykes (www.doctored.org.uk) provided technical editing services for the final drafts of this manuscript. Legal entity responsible for the study: The study protocol was approved by the ethics committee of Tabriz University (permit no. 5/d/988072). Funding: Hematology and Oncology Research Center, Tabriz University of Medical Science, Tabriz, Iran. Disclosure: All authors have declared no conflicts of interest.