Objective：To evaluate the value of multi-slice computed tomography (CT) in differential diagnosis of renal clear cell carcinoma and renal papillary carcinoma. Methods: The CT images of 47 patients with renal cell carcinoma (RCC) were reviewed. The RCC patients were divided into 2 groups pathologically, including 37 cases of clear cell RCC and 10 cases of papillary RCC. Plain scan and three phase (corticomedullary,nephrographic and excretory phases) CT were performed in all patients. Age and sex of patients, tumor size, enhancement degree and pattern (homogeneous, heterogeneous and predominantly peripheral), the presence of calcification or cystic degeneration (necrotic or hemorrhagic areas within the tumor) and tumor spreading (including perinephric change, venous invasion and lymphadenopathy) were compared between the 2 subtypes. Results: The degrees of enhancement were significantly different between the 2 subtypes in the corticomedullary, parenchymal and excretory phases (P＜0.05). Necrosis and cystic degeneration were more evident in the clear cell RCC than in papillary RCC regardless of tumor size (P＜0.05). A hypervascular pattern (higher tumor enhancement after contrast material injection due to higher vascularity) was noted in 21.6% of clear cell RCC cases and in 10% of papillary RCC (P＜0.05). Half of the clear cell RCC and 2.7% of papillary RCC patients showed homogeneous enhancement (P＜0.05). Calcification was evident in 21.6% of clear cell RCC patients and 20% of papillary RCC patients. Conclusion: The degree of enhancement is the most valuable parameter for differentiation of clear cell RCC and papillary RCC. The presence of cystic degeneration, hemorrhage, vascularity and enhancement patterns can also contribute to the differentiation of the 2 subtypes.