Currently, there is no accurate diagnostic molecular biomarker for renal cell carcinoma (RCC). The aim of this study was to assess the expression of microRNA-15a (miR-15a) in urine of patients with RCC and to evaluate its potential as a diagnostic molecular biomarker. In total, 67 patients with solid renal tumors were enrolled: clear-cell RCC (ccRCC, n = 22), papillary RCC (pRCC, n = 16), chromophobe RCC (chRCC, n = 14), oncocytoma (n = 8), papillary adenoma (n = 2) and angiomyolipoma (n = 5). MiRNA-15a expression levels measurement in urine were performed using qPCR. Urine of 15 healthy volunteers without kidney pathology was used as control. We observed a difference in mean miR-15a expression values in groups of pre-operative patients with RCC, benign renal tumors and healthy persons (2.50E-01 +/- 2.72E-01 vs 1.32E-03 +/- 3.90E-03 vs 3.36E-07 +/- 1.04E-07 RFU, respectively, p < 0.01). There was no difference in miR-15a expression between ccRCC, pRCC and chRCC (p > 0.05). Direct association between RCC size and miR-15a expression values was obtained (Pearson correlation coefficient-0.873). On the 8th day after nephrectomy, mean expression value in patients with RCC decreased by 99.53% (p < 0.01). MiR-15a expression differentiated RCC from benign renal tumors with 98.1% specificity, 100% sensitivity at a cut-off value of 5.00E-06 RFU, with AUC-0.955. MiR-15a expression measured in urine may be used as diagnostic molecular biomarker for RCC.