The aim of the study was to investigate possible associations of IL-6 gene polymorphisms (-596 A/G and -174 C/G) with cutaneous T-cell lymphoma (CTCL). In the case-control study, genotype distributions and allelic frequencies in two promoter IL-6 gene polymorphisms in the group of 63 Czech patients with CTCL were compared to those of 105 control non-CTCL subjects matched for age and sex. The IL-6 gene polymorphisms were determined by PCR with following restriction analysis. A significant difference of -596 A/G IL-6 genotype distribution was found between the CTCL patients and the controls (P = 0.002) with almost threefold odds ratio for the heterozygote (AG) genotype in CTCL patients (OR = 2.64, P = 0.002). No significant differences in genotype distribution and/or allelic frequency of functional -174 C/G IL-6 gene polymorphism were observed. The double heterozygote AGCG of both IL-6 promoter polymorphisms was associated with CTCL (OR = 2.24, 95% confidence interval 1.17-4.28, P = 0.01). Thus, the heterozygote variant of -596 A/G promoter IL-6 polymorphism could be considered as a genotype marker for CTCL.