Objective: Fine-needle aspiration cytology (FNAC) based on a liquid-based preparation is a safe and valuable diagnostic tool. However, due to unfamiliarity with this method and the considerably altered morphology that is associated with it, diagnosing renal cell carcinoma (RCC) from this type of preparation remains a challenge for cytopathologists. The aim of this study was to evaluate the cytomorphological characteristics of SurePath™ (SP)-based preparations compared with conventional smear (CS), and also the role of SP-based FNAC in the diagnosis of clear-cell RCC (CRCC), the most common primary renal malignancy. Study Design: Ex vivo FNAC of both tumors and normal renal parenchyma was prepared from 73 cases. Comparative cytomorphological analysis between liquid-based cytology (LBC) and CS as well as Fuhrman nuclear grading (FNG) was carried out. Immunocytochemistry was performed from normal and CRCC cytology specimens. Results: Normal renal cytology (NRC) showed no significant morphological differences between LBC and CS. For CRCC, LBC showed small, fragmented cell clusters, a 3-dimensional configuration, distinct cytoplasmic vacuoles, and irregular nuclear contours when compared with CS. FNG was overgraded with LBC compared to with CS. AMACR was the most valuable immunocytochemical marker for distinguishing CRCC from NRC. Conclusion: Once cytopathologists become familiar with the altered cytomorphological features of CRCC, FNAC, along with immunocytochemistry, may prove helpful for diagnosis.