Body fatness at young ages may be related to breast cancer risk independently of adult adiposity. The authors conducted a prospective analysis among 188,860 women (7,582 breast cancer cases) in the Nurses' Health Study (1988-2004) and Nurses' Health Study II (1989-2005) who recalled their body fatness at ages 5, 10, and 20 years using a 9-level pictogram (level 1: most lean; level 9: most overweight). Body fatness at young ages was inversely associated with risk of both premenopausal and postmenopausal breast cancer (per 1-unit increase in adolescent body fatness, relative risk (RR) = 0.88 and RR = 0.91, respectively; P(trend) < 0.0001). Among all women, the RR for adolescent body fatness of level 6.5 or higher versus level 1 was 0.57 (per 1-unit increase, RR = 0.90; P(trend) < 0.0001) and was unaffected by adjustment for current body mass index. The association was stronger for women with birth weights under 8.5 pounds (<3.9 kg) than for women with birth weights of 8.5 pounds or more (> or =3.9 kg) (per 1-unit increase, RR = 0.89 and RR = 0.94, respectively; P(interaction) = 0.04) and stronger for estrogen receptor-negative tumors than for estrogen receptor-positive tumors (per 1-unit increase, RR = 0.86 and RR = 0.92, respectively; P(heterogeneity) = 0.03). Body fatness at young ages has a strong and independent inverse relation to breast cancer risk throughout life.