Breast cancer has a complex genetic susceptibility. Innate and adaptive immunity can additionally increase the genetic risk to breast cancer development. We typed polymorphisms in the genes of the interleukin(IL)-1 and IL-17 proinflammatory cytokines in a case-control study in Caucasian population from Croatia. We compared the allelic and genotypic frequencies between patients (n=194), healthy women (n=188) and general population (n=531). The risk for breast cancer has been significantly different at both allelic and genotypic levels for two polymorphisms: the IL1B gene single nucleotide polymorphism (SNP) at -511 (G>A; rs16944) and the IL1 Receptor antagonist gene (IL1RN) variable number of tandem repeats (VNTR). Themajor allele (G) of the IL1B rs16944 SNPwas associated with susceptibility to breast cancer (P<0.01) in general populationwith odds ratio (OR) of 1.42 and 95 % confidence interval (CI) at 1.09–1.85. The IL1RN VNTR allele 3 (5 repeats) was correlated with predisposition to disease (P<0.01,OR: 9.71, 95%CI: 1.34–198.51) inwomen. At the genotype level, G/G homozygosity at IL1B rs16944 was significantly associated with predisposition to disease (P<0.02, OR: 1.68, 95 % CI: 1.10–2.57), whereas the heterozygosity (G/A) was correlatedwith protection to disease (P<0.01, OR: 0.57, 95 % CI: 0.37–0.89) in women. The IL1RN VNTR genotype 1/3 was significantly associated with susceptibility to breast cancer (P<0.01, OR: 10.01, 95 % CI: 1.37–207.55). Genotypic differences were also significantly different in comparison with general population for IL1B SNP (P<0.001) and IL1RN VNTR (P<0.01). These results corroborate a premise that inflammatory factors play a role in pathogenesis to breast cancer.