Interleukins and cytokines are important regulator of the aetio-pathogenesis of the majority of cancers. Mechanistic role of IL-1RN and IL-4, particularly in breast carcinogenesis, is well documented. However, the role of polymorphisms of IL-1RN and IL-4 combinations associated with risk of breast cancer is not reported. The IL-1RN and IL-4 gene polymorphisms were genotyped with VNTR-PCR in 100 patients (benign tumor n = 32 and breast cancer n = 68) and 200 normal healthy control subjects with normal mammogram. Genotype distribution and allelic frequencies between patients and controls were compared and odds ratios (OR) with 95% confidence intervals (CI) were calculated using SPSS software (version 12.0). There were no significant differences in the genotype distributions of both IL-1RN and IL-4 polymorphisms between cases and controls. Similarly, subgroup analysis showed that there is no significant association for pre- and postmenopausal women. However, BB genotype of IL-1RN significantly differs among benign and malignant stages of breast cancer. IL-1RN and IL-4 polymorphisms alone or in combination are not associated with risk of breast cancer in Indian patients. The association of IL-1RN with malignant stages may indicate its possible role in progression of breast cancer. Further studies in other population are needed to confirm our findings and to elucidate the role of IL-1RN in progression of breast cancer.