The cytokine interleukin-1β (IL1B) is important for anti-tumour immune response. Genetic variation may modify the expression of IL1B and thereby influence the risk of disease. We investigated genetic variations with functional importance in the IL1B and NFKB1 genes in 348 population-based samples of multiple myeloma (MM) and a random sample of 1700 individuals. Carriers of the variant T-allele IL1BC-3737T and carriers of the TGT haplotype were at lower risk of MM [relative risk (RR) 0·58 (95% confidence interval (CI) = 0·41–0·84) and RR 0·59 (95%CI 0·40–0·85), respectively]. No association with risk of MM was found for the NFKB1- 94 ins/del polymorphism.