E26 transformation-specific (ETS) transcription factors have become increasingly recognized as key regulators of differentiation, hormone responses and tumorigenesis in endocrine organs and target tissues. The ETS family is highly diverse, consisting of both transcription activators and repressors that mediate growth factor signaling and regulate gene expression through combinatorial interactions with multiple protein partners on composite DNA elements. ETS proteins have a role in the endocrine system in establishing pituitary-specific gene expression, mammary gland development and cancers of the breast, prostate and reproductive organs.