The CCAAT/enhancer binding protein (C/EBP) family of bZIP transcription factors control the proliferation and differentiation of a variety of tissues. While C/EBPalpha and -delta are also expressed in the mammary gland, the multiple protein isoforms of C/EBPbeta appear to play a critical role in mammary gland development and breast cancer. Targeted deletion of all the C/EBPbeta isoforms results in a severe inhibition of lobuloalveolar development and a block to functional differentiation, as well as more subtle changes in ductal morphogenesis. The altered expression of a number of molecular markers, including the progesterone, estrogen, and prolactin receptors, the transporter proteins (NKCC1 and aquaporin 5), and several markers of skin differentiation (Sprr2A and keratin 6), suggests that germline deletion of C/EBPbeta results in an altered cell fate. Thus, C/EBPbeta appears to play a role in the specification of progenitor cell fate not only in the mammary gland, but also in a number of other tissues.