Objective To evaluate the trends in urine aquaporin-1 (AQP1) and perilipin 2 (PLIN2) concentrations in patients with clear cell and papillary renal cell carcinoma (RCC), we determined the relationship between the urine concentration of these biomarkers and tumor size, grade, and stage. Materials and Methods The biomarker concentrations were determined by sensitive and specific Western blot procedures normalized to the urine creatinine excretion. The analysis included 61 patients undergoing partial or radical nephrectomy for clear cell or papillary RCC and 43 age- and sex-matched control patients. Relationships between urine biomarker concentrations and tumor size, stage, and grade were assessed. Results Patients with RCC had 35-fold and 9-fold higher median urinary AQP1 and PLIN2 concentrations, respectively, compared with controls. Both tumor markers decreased after tumor resection to concentrations equivalent to those of controls. The sensitivity and specificity were both 100% for AQP1 and 92% and 100%, respectively, for PLIN2. A significant linear correlation was found between the tumor size and the prenephrectomy AQP1 (Spearman coefficient 0.78, P <.001) and PLIN2 (Spearman coefficient 0.69, P <.001) concentrations. A correlation was found for both markers with tumor stage (overall P =.030), when the stage was dependent primarily on the tumor size (stages T1 and T2), but not with stage T3, which reflected extrarenal spread. Neither marker showed a significant correlation with tumor grade. Conclusion AQP1 and PLIN2 were significantly increased in patients with clear cell and papillary RCC compared with controls. The preoperative urinary concentrations of these markers reflected the tumor size and stage.