Nuclear factor of kappaB (NF-kappaB) is a group of sequence-specific transcription factors that is best known as a key regulator of the inflammatory and innate immune responses. Recent studies of genetically engineered mice have clearly indicated that NF-kappaB is also required for proper organogenesis of several epithelial tissues, including the mammary gland. Mice have shown severe lactation deficiency when NF-kappaB activation is specifically blocked in the mammary gland. In addition, there are strong suggestions that NF-kappaB may play an important role in the etiology of breast cancer. Elevated NF-kappaB DNA-binding activity is detected in both mammary carcinoma cell lines and primary human breast cancer tissues.