TBX2 and TBX3 are members of a family of genes encoding developmental transcription factors, characterized by a 200 amino acid DNA binding domain (T-box). Tbx2 and Tbx3 are closely related T-box proteins that have been implicated in development of a number of different tissues including the mammary gland. TBX3 is required for normal mammary development in mouse models and in patients with ulnar-mammary syndrome (UMS). In addition to a role in development, TBX2 and TBX3 have been implicated in tumor development through downregulation of the alternative reading frame (ARF) tumor suppressor and an associated bypass of senescence. Here we review the current information on the roles of Tbx2 and Tbx3 in mammary gland development and tumorigenesis.