We studied plasma levels of IL-10 and five single nucleotide polymorphisms in the interleukin-10 (IL-10) gene promoter in patients with Hodgkin lymphoma (HL) to address potential genotype-phenotype correlations. Patients with elevated IL-10 levels were more likely to have advanced stage disease and inferior event-free survival. Homozygous carriers of the variant alleles at position -592 (AA) and -1082 (GG) of the IL-10 promoter had higher IL-10 plasma levels, independent of male gender and advanced stage of disease which also determined increased IL-10 production. This analysis indicates that the genetic background can modulate plasma levels of IL-10, and ultimately prognosis in HL.