Associations of body fat and body fat distribution with breast cancer were studied in 16,355 postmenopausal women with a natural menopause, aged 49 to 68 years, participating in a breast cancer screening project (the Diagnostic Investigation of Mammary Cancer [DOM] project in Utrecht, The Netherlands). One hundred nineteen women had breast cancer detected at first screening. Fat distribution was assessed by contrasting groups of subscapular and triceps skinfold thickness. No relationship between fat distribution and breast cancer was found. After adjustment for age, women in the highest quartile of Quetelet's index (QI) (weight/height2) had an odds ratio of 1.65 (95% confidence interval [CI], 0.97 to 2.81) compared with women in the the lowest quartile (test for trend, P less than 0.05). For subscapular skinfold and triceps skinfold, the odds ratios were 2.23 (95% CI, 1.28 to 3.91) and 2.01 (95% CI, 1.21 to 3.32), respectively, comparing the highest with the lowest quartile. The authors conclude that in postmenopausal women, overall obesity is associated with increased risk of breast cancer, whereas fat distribution, as measured by contrasting groups of subscapular and triceps skinfold thicknesses, is not related to breast cancer.