The McCune-Albright syndrome (MAS) is characterized by a clinical triad of polyostotic fibrous dysplasia, café-au-lait hyperpigmented macules, and hypersecretory endocrinopathies. Acromegaly is an uncommon manifestation of the endocrine disturbance associated with MAS, and the role of surgery in managing these cases has been a topic of debate. The authors present the case of a 35-year-old man with MAS who was also diagnosed with acromegaly, hyperprolactinemia, and pituitary macroadenoma. The patient had an 18-year history of fibrous dysplasia involving the right frontal bone and ribs as well as multiple endocrinopathies, but no cutaneous hyperpigmented macules. An oral glucose tolerance test demonstrated partial suppression of plasma levels of growth hormone (GH). The patient underwent transsphenoidal resection of the pituitary tumor, performed with assistance of neuronavigation, and tolerated the procedure well. After the surgery, both prolactin and GH levels returned to normal. These results suggest that neuronavigation-assisted transsphenoidal surgery can safely remove pituitary adenomas associated with MAS and successfully treat the underlying endocrine abnormalities.