Matrix metalloproteinase-9 (MMP-9) plays a pivotal role in cancer invasion and metastasis. Recently, experimental study has shown that MMP-9 is also implicated in early carcinogenesis. We hypothesized that MMP-9 polymorphisms influence the predisposition to develop renal cell carcinoma (RCC). To test the hypothesis, we determined MMP-9 C-1562T and R279Q genotypes in Japanese RCC cases (n=179) and controls (n=211). Furthermore, we investigated the relationship between MMP-9 polymorphisms and clinicopathological features. The distribution of C-1562T and R279Q genotypes was not significantly associated with the risk of RCC (odds ratio [OR]=1.14, 95% confidence interval [CI]=0.73-1.77 for -1562 CT/TT genotypes versus CC genotype; OR=1.29, 95% CI=0.86-1.93 for 279 RQ/QQ genotypes versus RR genotype). However, the distribution of R279Q genotypes was significantly associated with the histological grade (P<0.01). The present results suggest that MMP9 R279Q polymorphism has influence on the malignant potential of RCC.