We evaluated the clinical usefulness of plasma matrix metalloproteinase-7 (MMP-7) as a diagnostic and prognostic biomarker in patients with renal cell carcinoma (RCC). MMP-7 was quantified in plasma of 50 healthy subjects and 97 RCC patients using a Fluorokine MultiAnalyte Profiling assay. RCC patients were stratified into the following groups: without metastases (N0M0; n = 39), with lymph nodes (N1M0; n = 13), and with distant metastases (M1; n = 45). Diagnostic performance of MMP-7 was analyzed by the receiver operating characteristics (ROC) curve. Kaplan-Meier analysis and the Cox regression model were used to estimate the impact of MMP-7 on the cancer-specific survival outcome of RCC patients. MMP-7 was significantly higher in both metastatic groups N1M0 and M1 (medians, 3.82 and 3.34 microg/L) compared to N0M0 group or controls (medians, 1.85 and 1.64 microg/L; all P < 0.001). In ROC analysis, the area under the ROC curve of MMP-7 was 0.80 in the detection of metastases in RCC (P < 0.0001). In the Kaplan-Meier analysis, patients with MMP-7 above the 95th percentile of controls showed less favorable survival rates compared to those with normal MMP-7 (log-rank test, 15.7; P < 0.0001). High MMP-7 was associated with cancer-related mortality estimated by univariate Cox regression (risk ratio, 4.34, 95% CI, 1.12-10.6; P = 0.032). The multivariate Cox regression model determined MMP-7 (risk ratio, 2.70, 95% CI, 1.39-5.24; P = 0.003) and metastases (risk ratio, 5.81, 95% CI, 2.77-12.2; P < 0.0001) as independent determinants of cancer-related survival outcomes. In conclusion, increased plasma MMP-7 could be related to metastatic disease and poor prognosis in patients with RCC.