Background: The enhancer of zeste homolog-2 is overexpressed in many human cancers. High CD8+ T cell density was associated with favorable prognosis in various tumors, but this isn’t true for all cancers. Nuclear grading of RCC is an important prognostic factor but it is subjective. Automated nuclear morphometry is more accurate. Aim: Evaluation of EZH2 expression, CD8+ density, and nuclear morphometry in RCC. Methods: In this retrospective study, IHC staining of EZH2 and CD8+ was done and assessed for each RCC case. CD8+ density was calculated. Quantitative nuclear morphometry was done by automated image analysis. Results: EZH2 expression showed highly significant relation with histologic grade(P=0.002), and AJCC stage(P=0.004)& showed significant relation with tumor extent(P=0.012), nodal metastasis (P=0.033), and distant metastasis(P=0.044). Highly significant relation between CD8+ density and histologic types(P=0.0001), histologic grade (P