We have investigated the expression of two estrogen receptor h (ERh) isoforms, ERh1and ERh5, which activate gene transcription independent of estrogen or growth factors, in ERa-negative breast cancer tissues.We report here, for the first time, that ERa-negative tissues express significant levels of ERh1 and ERh5, and their expression levels are not different from levels in ERapositive tumors. However, significant differences exist between the two racial groups, African American and Caucasian, in that the patients from the former group express higher levels of ERh1and ERh5 but not ERa. These two transcription factors could be potential molecular targets for designing chemopreventive drugs to treat ERa-negative breast cancers.