Obesity is implicated in breast cancer risk and progression and is associated with poor prognosis in both pre- and post-menopausal incidence of the disease. In particular, the risk of developing breast cancer increases with higher body mass index (BMI) in post-menopausal women. Industrial societies, such as the US, have moved to consumption of diets enriched in fat leading to a positive energy balance, making obesity a national crisis. Significant amounts of saturated fats in the diet have been replaced by polyunsaturated fats (PUFA), particularly the n-6 fatty acids of vegetable oils to decrease cardiovascular risk factors. We sought to study the influence(s) of specific dietary fatty acids on the development of mammary tumors in female rats. Female rats exposed to the diets in utero were dosed with a mammary carcinogen: dimethylbenz[a]anthracene (DMBA) at weaning (DOW) and at puberty (Day of Life DOL 50) and followed for 3 months to monitor tumor development. The diets contained either 10% or 40% fat (% kcal) of one of these fatty acids: olive oil, safflower oil or butter fat. For those rats dosed at DOW, there were statistically (P<0.05) greater number of carcinoma in situ (CIS) and invasive carcinoma (INV) lesions present in rats consuming the 40% olive oil (HFO) and 40% Butter (HFB) diets compared to the control diet. The tumor latency (time to first lesion detected) was shorter (43.4 days) for rats consuming the HFO diet compared to those rats consuming other diets. Additionally 90% of rats on the HFO diet dosed with DMBA at DOW developed more than 2 mammary lesions compared to 75% or less for other diets (45% for AIN). Our findings suggest that HFO and HFB may enhance susceptibility to carcinogenesis through their interaction with obesity. Obesity facilitates the production and availability of numerous mitogenic agents, (including estrogen and IGF-1), immune modulators (including leptin and IL-6), and angiogenic factors (including vascular endothelial growth factor and hepatocyte growth factor) to susceptible target cells throughout the body. Additionally, obesity is associated with increased inflammation and inflammatory markers such as NF-kB and its regulated genes which are involved in invasiveness, proliferation, angiogenesis, and inflammation. Therefore, we will present data suggesting HFO and HFB increase carcinogenesis by influencing obesity and inflammation. These findings begin to suggest mechanisms by which nutrients can influence mammary carcinogenesis.