Purpose: To analyze the prognostic value and potential target for therapeutic intervention of enhancer of zeste homologue 2 (EZH2) in uveal melanomas (UM) patients. Method: We analyzed EZH2 expression in 89 primary UM patients by immunohistochemistry to observe the clinicopathological and prognostic value of EZH2. Results: The high levels of mitoses count and Ki67 labeling index had significant correlation with overexpression EZH2 (R = 0.408, P<0.0001; R = 0.72, P<0.0001). High level of EZH2 expression was significantly associated with increased risk of distant metastasis by the Cox proportional hazards regression model (multivariate hazard ratio: 2.12; log rank P = 0.037) and shorter UM-specific survival (multivariate hazard ratio: 3.92; log rank P = 0.036). Conclusion: Our critical finding is that overexpression EZH2 in UM can be served as predictive marker and is associated with adverse clinical outcomes. Further observation of EZH2 as a potential therapeutic target in UM is necessary.