Broad cross-talk exists between the endocrine and immune systems. Estrogen receptor expression in lymphocytes suggests that hormonal modulation may influence lymphoma risk. Analysis of genetic polymorphisms that affect oestrogen production, such as cytochrome P450 17A1 (CYP17A1) −34T>C, may provide insight into oestrogen's role in lymphomagenesis. CYP17A1−34T>C and CYP17A1 IVS2 105A>C polymorphisms were analyzed in a non-Hodgkin lymphoma (NHL) population-based case–control study. The CYP17A1−34CC genotype was positively associated with NHL [odds ratio (OR) = 1·44, 95% confidence interval (CI) 1·02–2·03], particularly diffuse large B-cell lymphoma (OR = 1·76, CI 1·14–2·71). Associations of CYP17A1 polymorphisms with increased risk of NHL suggest a role for oestrogen in lymphomagenesis.