The precise benefit and safety of pazopanib in non-clear cell renal cell carcinoma (nccRCC) has not yet been elucidated. Therefore, the aim of the present study was to investigate the role and safety profile of pazopanib in nccRCC. A total of 40 nccRCC patients treated with pazopanib were enrolled. Progression-free survival (PFS), and overall survival (OS) times were analyzed with Kaplan-Meier method. Univariable and multivariable Cox regression models were used to identify the predictive factors for PFS, and OS. The primary endpoint was the response assessment of pazopanib according to Response Evaluation Criteria in Solid Tumors in non-ccRCC pa - tients. The median age of patients was 62 (range: 45-78). Considering histologic subtypes, the numbers of papillary, chromophobe, sarcomatoid differentiation and unclassified type were 21 (52.5%), 6 (15%), 5 (12.5%), and 8 (20%), respectively. The median PFS, and OS in all cohort were 13.8 (95% CI: 0-30.7), and 45.6 months (95% CI: 24.3-66.9), respectively. The overall response rate (complete response+partial response), and disease control rate (complete response+partial response+stabil disease) were 45%, and 77.5%, respectively. Grade 3 or more adverse effects that were managed with dose reduction, and treatment delay effectively were observed in 16 (40%) patients. The independent determinants that were associated with PFS and OS in the multivariate analyses were IMDC scoring system (p= 0.001), lactate dehydrogenase (LDH) level (p= 0.015) for PFS, and only IMDC scoring system (p< 0.001) for OS. Pazopanib can be used as an effective agent with tolerable safety profile for the treatment of advanced nccRCC patients.