BACKGROUND The McCune-Albright syndrome (MAS) is a complex congenital disorder caused by the embryonic post-zygotic somatic activating mutations in the GNAS1 gene. In such syndrome, phenotypes are heterogeneous and comprised polyostotic/monostotic fibrous dysplasia, café au lait macules, and hyperfunctioning endocrinopathies as the excess growth hormone. Likewise, acromegaly, as a manifestation of the endocrine hyperfunction, is unusual and affects about 20% of patients with MAS. METHODS This research study describes a case of a 31-year-old female subject presenting polyostotic fibrous dysplasia with severe facial involvement, along with acromegaly and the MAS. The case was satisfactorily managed by surgical re-alignment and presented no clinical signs of relapse in a 12-year follow-up period. Finally, a literature review was conducted to discuss the standard protocols and the controversies when treating such cases. CONCLUSIONS Patients with craniomaxillofacial fibrous dysplasia associated with acromegaly may present significant facial deformities that can be satisfactorily treated by cosmetic treatment, especially in patients with psychological problems and severe social acceptance.