We have been investigating gene-expression profiles in estrogen receptor (ER)-negative breast cancers to identify molecules involved in breast carcinogenesis and to select genes or gene products that might be useful as diagnostic markers or targets for new molecular therapies. Here we report evidence that the gene encoding retinoic acid-induced protein 3 (RAI3) is a potential molecular target for treatment of breast cancers. Using quantitative reverse transcription-PCR (RT-PCR), we documented increased expression of RAI3 in 19 of 25 primary breast cancers and in 6 of 11 breast-cancer cell lines examined, by comparison with normal mammary-gland tissue. Treatment of human embryonic kidney (HEK293) cells with siRNA against RAI3 suppressed expression of RAI3 and also suppressed cell growth. Transfection of siRNA into breast-cancer cell lines MCF7 and T47D also suppressed RAI3 mRNA and growth of the cancer cells. Because our data imply that up-regulation of RAI3 function is a frequent feature of breast carcinogenesis, we suggest that selective suppression of signal from RAI3 might hold promise for development of a new strategy for treating breast cancers.