McCune-Albright syndrome (MAS) is characterized by the clinical triad of polyostotic fibrous dysplasia, cafe-au-lait pigmented skin lesions, and multiple endocrinopathies. The molecular basis of MAS is a mutation in G(s)alpha that results in constitutive activation of adenylyl cyclase in affected tissues. This mutation occurs during early embryogenesis, and therefore patients with MAS are mosaic. The identification of activating mutations of Gsa in liver, heart, and gastrointestinal tract of patients with MAS suggests a broader spectrum of clinical disease than previously appreciated.