To investigate whether single nucleotide polymorphisms (SNPs) in key cytokine and innate immunity genes influence risk for childhood lymphomas, we genotyped 37 children with Hodgkin's (HL) and 48 with non-Hodgkin's lymphoma (NHL), aged (1 month-14 yr), along with their 85 age- and gender-matched controls suffering from mild medical conditions. Genotypic analysis was performed for 10 SNPs from nine genes with important role in immunoregulatory pathways (IL4, IL4R, IL6, IL10, IL12, IL18, TNFalpha, IFNgamma, CD14). Analysis of SNPs genotypes revealed that the CD14 -159 C>T polymorphism was associated with significantly increased risk for HL regarding both the CC and CT genotypes (OR(CC): 5.36; 95% CI, 1.30-22.14; P = 0.02, OR(CT): 3.76; 95% CI, 1.00-14.16; P = 0.05). An indicative association between IL18-137 G>C polymorphism with the CC genotype and NHL did not reach, however, statistical significance (OR(CC), 3.78; 95% CI, 0.87-16.38; P = 0.08). In conclusion, our findings suggest that genetic variation in the CD14-159 loci may be associated with childhood HL risk; these preliminary findings need to be further confirmed in sizeable multi-centre studies along with determination of cytokines, which could provide an insight on the biologic basis underlying these findings.