Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis and cancer progression. The VEGF genetic polymorphisms were shown to be independently associated with an adverse outcome in various malignancies. We investigated the possible associations of two polymorphisms (-2578C/A and +936C/T) in the VEGF gene with the clinicopathologic parameters for patients with non-Hodgkin's lymphoma (NHL). We studied the genotype and allele frequencies of the -2578C/A and +936C/T polymorphism in DNA samples of 431 patients with NHL using restriction fragment length polymorphism typing analysis. The -2578A allele was significantly associated with less frequent clinical staging III, IV and bone marrow involvement (The odds ratio (OR) 0.59; 95% confidence interval (CI) 0.43-0.82; and OR 0.66; 95% CI 0.48-0.91, respectively). The CA and CA + AA genotype of the -2578C/A were significantly associated with less frequent bone marrow involvement than CC genotypes (OR 0.57; 95% CI 0.38-0.86; and OR 0.57; 95% CI 0.39-0.85, respectively). The TT genotype of the +936C/T polymorphism was significantly associated with less frequent T cell histological type, clinical staging III, IV and bone marrow involvement (OR 0.25; 95% CI 0.07-0.89; OR 0.37; 95% CI 0.15-0.89; and OR 0.31; 95% CI 0.10-0.96, respectively). The +936 T allele was marginally associated with less frequent bone marrow involvement and with Clinical staging III, IV (OR 0.71; 95% CI 0.49-1.01; and OR 0.70; 95% CI 0.49-1.00, respectively). None of the evaluated genotypes of -2578C/A was significantly associated with the gender, age, tumor size, B symptoms and immunohistological subtype. No significant associations between the genotype of +936C/T and the clinicopathologic variables, gender, age, tumor size and B symptoms were ascertained. Both of the -2578C/A and +936C/T polymorphisms were not related to the patients' overall survival. We present the first data on VEGF gene polymorphisms in NHL. Our findings support the hypothesis that the -2578 CA and CA + AA and +936 TT VEGF genotypes and -2578A and +936T alleles are associated with decreased risk for invasion. But the investigated VEGF gene polymorphisms were not associated with prognosis in patients with NHL.