Common polymorphisms in genes encoding for cytokines implicated in the inflammatory response and Th1/Th2 balance might play a role in the development and prognosis of chronic lymphocytic leukaemia (CLL). To test the hypothesis, we investigated 13 single nucleotide polymorphisms (SNPs) in nine of such genes in a population-based case-control study, conducted in the Italian region of Sardinia in 1999-2003. Forty incident CLL cases and 113 population controls were available for study. The following SNPs were selected:IL1A-889C>T, IL1RN 9589A>T, IL1B-31C>T, IL1B-511C>T, IL2-384T>G, IL6-174G>C, IL6-597G>A, IL10-1082A>G, IL10-3575T>A, TNF-308G>A, LTA-91A>C, LTA 252A>G andCARD15 nt1007. After adjusting by age and gender, individuals homozygous for theIL1B-511T allele run a lower risk of CLL (OR=0.1, 95% CI 0.0, 0.8,p=0.032), while risk showed a 4.5-fold increase associated with the genotype homozygous for theIL6-174C allele (OR=4.5; 95% CI 1.1, 19.3,p=0.041). Individuals homozygous for theIL6-174C allele and carrying the homozygousIL1B-511C allele showed an 11-fold increase in CLL risk (OR=11.4, 95% CI 1.9, 69.4,p=0.008). None of the other interleukin SNPs evaluated showed any association with CLL risk. Large multicentre pooled studies are warranted, achieving the statistical power required to confirm whether IL6 and IL1B gene polymorphisms might play a role in CLL development and prognosis, as well as the null associations herein reported.