It is suggested that a large breast size among women may predict type 2 diabetes risk independent of BMI and waist circumference (WC). The purpose of this study was to determine the independent associations of breast volume with cardiometabolic risk factors and regional fat distribution. A total of 92 overweight or obese premenopausal women (age = 39.9 +/- 6.8 years) underwent full-body magnetic resonance imaging (MRI) for the assessment of breast volume, visceral adipose tissue (VAT), abdominal and lower-body subcutaneous AT (SAT), and intermuscular AT (IMAT), a 2-h oral glucose tolerance test (OGTT), and fasting phlebotomy for assessment of triglyceride, total, high-density lipoprotein-, and low-density lipoprotein-cholesterol levels. Breast volume was not associated with any of the cardiometabolic risk factors assessed (P > 0.05). However, VAT was consistently associated with a number of cardiometabolic risk factors (OGTT glucose, OGTT insulin, and triglyceride levels) after controlling for age, BMI, WC, breast volume, and the other AT depots. In univariate models, breast volume was positively associated with VAT, IMAT, and abdominal and lower-body SAT (P < 0.05). After controlling for age, BMI, and WC level, breast volume remained positively associated with VAT and IMAT (P < 0.05), such that women with the highest breast volume had approximately 1.1 and 1.3 kg more VAT and IMAT, respectively, but no more abdominal or lower-body SAT, by comparison to women with the smallest breast volume. Thus, the previously documented association between breast size and type 2 diabetes risk may be in part explained by excess VAT and/or IMAT deposition.