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Summary Background The aim of the study was to investigate the association of paraoxonase 1 (PON1) polymorphism, PON1/arylesterase (ARE) activity and oxidative stress index (OSI) in breast cancer (BC) patients with type 2 diabetes (DM). Methods Our study group consisted of 30 healthy women (HV group) and 66 female BC patients. The BC patients were divided into two groups: those with (n=37) and without DM (n=29) (BDM and NBDM group). Genotyping of PON1 Q192R and L55M polymorphisms were done by polymerase chain reaction (PCR) – restriction fragment length polymorphism (RFLP) method. Serum PON1/ARE enzyme activities, total oxidant status (TOS) and total antioxidant status (TAS) were analysed by spectrophotometric method. The ratio of TOS to TAS was accepted as the oxidative stress index (OSI). Results PON1 Q192R genotype frequency distribution was significantly different in the BDM group compared to the NBDM group (p=0.021). When alleles distribution was examined, R and L alleles were significantly lower, Q and M alleles were significantly higher in the BDM group than in the NBDM group (p<0.001). TOS and OSI were statistically higher in BC patients than HV group (p<0.001). Conclusions Our results suggest that PON1 gene Q and M alleles may be the risk factors predisposing formation of BC due to increased oxidant damage seen in DM. However, these statements require further confirmation with screening PON1 polymorphism in a greater number of patients with DM, and also wide range follow-up studies are necessary for the same purpose.