The objective of this case-control study was to investigate the relationship between purposeful physical activity, body fat distribution, body mass index, and steroid hormones. These factors are known to be implicated in modulating breast cancer risk in premenopausal women. A total of 112 newly diagnosed, premenopausal breast cancer patients and 106 age-matched premenopausal disease-free controls were admitted to the study. Information regarding personal, medical, hormonal, and reproductive history, smoking and alcohol use, physical activity history, and anthropometric measurements was obtained. Serum samples for steroid hormone assays were collected and analyzed. Disease-free premenopausal controls had a significantly higher physical activity index (PAI) (p</=0.05), however, significantly higher weight (p</=0.05), body mass index (BMI) (p=0.01), waist (p</=0.005) and hip (p</=0.05) circumferences, waist:hip ratios (p</=0.05), and serum total estradiol levels (p<0.0005) were observed in cancer cases. The final model using stepwise logistic regression analysis indicates that the variables that significantly predicted breast cancer risk were waist:hip ratio (odds ratio [OR]=1.11, p</=0.005) and serum total estradiol levels (OR=1.03, p</=0.0001). Our study provides some evidence that purposeful physical activity may reduce upper body fat distribution associated with adult weight gain. This may be a result of alterations in the steroid hormone pathway, such as reduced estradiol levels. This demonstrates the potential mechanism through which increased physical activity can reduce the risk for breast cancer in premenopausal women.