The pathophysiology of Non-Hodgkin's lymphoma (NHL) is still unknown and clinical course is very unpredictable. Many cytokines, including interleukin-10 (IL-10), play a role in the perpetuation of this disease. The IL-10-producing capability has been found to be influenced by the IL-10 gene promoter polymorphisms. The aim of the present study was to assess whether any of IL-10(−1082 A/G, −819 C/T and −592 A/C) genotypes prevails in Polish patients with NHL and whether IL-10 promoter polymorphisms may be associated with less or more favourable course of the disease. IL-10 gene promoter polymorphisms were assessed in 105 individuals, including 55 NHL patients and 50 ethically matched controls. The frequency of the IL-10 low-producing −1082 AA homozygous genotype was significantly higher in patients with aggressive NHL as compared with patients with indolent forms of the disease (0.57 vs 0.28, P< 0.05) and controls [0.57 vs 0.32, odds ratio (OR) = 2.69, P< 0.05]. Also, the presence of the ACC genotype was more frequently detected among patients with more aggressive disease than in those with indolent forms (0.74 vs 0.47, P< 0.05) and healthy controls (0.74 vs 0.42, OR = 3.69, P< 0.05). In multivariate analyses, the AA homozygosity (OR = 6.33, P< 0.05) and ACC genotype (OR = 3.57, P= 0.05) appeared as independent risk factors of more aggressive manifestation of NHL in addition to the elevated lactate dehydrogenase 480 level. Although no direct association was found between IL-10 promoter polymorphisms and NHL, IL-10 (−1082) AA homozygosity and IL-10 ACC genotype were found to be associated with unfavourable prognosis in patients with NHL.