An initial analysis of data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registries shows that the age-adjusted incidence rate of breast cancer in women in the United States fell sharply (by 6.7%) in 2003, as compared with the rate in 2002. Data from 2004 showed a leveling off relative to the 2003 rate, with little additional decrease. Regression analysis showed that the decrease began in mid-2002 and had begun to level off by mid-2003. A comparison of incidence rates in 2001 with those in 2004 (omitting the years in which the incidence was changing) showed that the decrease in annual age-adjusted incidence was 8.6% (95% confidence interval [CI], 6.8 to 10.4). The decrease was evident only in women who were 50 years of age or older and was more evident in cancers that were estrogen-receptor-positive than in those that were estrogen-receptor-negative. The decrease in breast-cancer incidence seems to be temporally related to the first report of the Women's Health Initiative and the ensuing drop in the use of hormone-replacement therapy among postmenopausal women in the United States. The contributions of other causes to the change in incidence seem less likely to have played a major role but have not been excluded. Copyright 2007 Massachusetts Medical Society.