Metabolic syndrome (MS), characterized by central adiposity, insulin resistance, low serum high density lipoprotein cholesterol (HDL-C), high serum triglycerides, and high blood pressure, seems to be in strict correlation to breast carcinogenesis [1, 2]. MS, according to the National Cholesterol Program (NCEP) Adult Treatment Panel III (ATP III), can be defined as the presence of at least three of the following clinical criteria: waist circumference >88 cm in women, HDL-C <50 mg/dl, blood pressure ≥130/85 mmHg, triglyceride >150 mg/dl and insulin resistance . The prevalence of MS is high in the general population with approximately 34% of adults meeting the above-mentioned criteria and increases with age and body mass index (BMI). In fact, women over 60 years and overweight or obese are much more likely to meet the MS criteria . Consistently, post-menopausal women are often affected by MS and, interestingly, show the highest incidence of breast cancer in the female population . Although many epidemiological studies link obesity and MS to the increased frequency of many cancer types, the molecular mechanisms underlying this increased risk are still poorly characterized. Visceral adipose tissue has multiple endocrine, metabolic and immunological functions and has been shown to be central in the MS pathogenesis. MS is a pro-inflammatory, pro-coagulant state associated with insulin resistance [5, 6]. The increase in adipose tissue mass, which characterizes MS, can have both direct and secondary effects favouring tumorigenesis . Obese patients often develop insulin resistance with various tissues showing low cell sensitivity to insulin activity. As a consequence, a balancing mechanism stimulates insulin release resulting in a chronic compensatory hyperinsulinemia. By continuously stimulating insulin signalling in sensitive tissues, high levels of circulating insulin cause aberrantly increased mitogenic and antiapoptotic effects . Although the obese state generates peripheral insulin resistance in many tissues, not all insulin signalling is impaired. In the diabetic liver, the gluconeogenic pathway becomes insulin resistant, and insulin-stimulated lipogenesis remains sensitive. Thus, in insulin-resistant patients, specific tissues and signalling pathways can remain insulin-sensitive and are exposed to higher than normal levels of insulin signalling. Initial experiments demonstrated that in human breast cancer cell lines insulin has been shown to promote DNA synthesis, suggesting a mitogenic effect . When insulin concentrations are high, insulin — which is structurally similar to insulin-like growth factor 1 and 2 (IGF1 and IGF2) — acts also as a growth factor by binding the IGF-receptors (IGF1R and IGF2R) [8, 9]. Moreover, increased insulin signalling can induce overexpression of the receptors . Consistently, in vitro and in vivo studies have shown insulin receptor overexpression in breast tissue. Furthermore, it seems that high insulin levels can alter the levels of IGF-binding proteins, which regulate the amount of bioactive insulin or IGFs in the microenvironment, thereby resulting in impaired insulin signalling . As various epidemiological studies associated type 2 diabetes with increased incidence of various cancer types, including breast cancer, we wondered what is the specific contribution of insulin resistance in breast carcinogenesis at the clinical level [10–12]. To this aim we compared breast cancer patients to healthy women in order to assess whether a correlation exist with MS criteria and, specifically, insulin resistance measured through Homeostasis Model Assessment (HOMA-IR).