Background: Although pituitary adenoma is one of the most common intracranial tumors, it rarely progresses secondarily into a metastatic carcinoma. Commonalities in reported cases include subtotal resection at presentation, treatment with radiation therapy, and delayed metastatic progression. Pathologic descriptions of these lesions are varying and inconsistent. Case Description: A 52-year-old male was diagnosed with acromegaly and pituitary tumor in 1996. He underwent four subtotal resections and five courses of stereotactic radiosurgery over 14 years. He developed left eye lateral gaze palsy, and was found to have a distant orbital metastasis with involvement of the left lateral rectus and lateral orbital wall. He underwent left orbital craniotomy via eyebrow incision for resection of this lesion. Pathologic evaluation showed a markedly elevated Ki67 level of 30%. Conclusion: While overall incidence of metastatic progression of pituitary adenoma after radiotherapy appears to be low, it appears to be a possible complication, and could be more likely in patients receiving multiple doses of radiotherapy. Our review of reported cases showed that 45/46 (97.8%) of patients developing carcinoma had prior radiation exposure. These patients may also have more aggressive pathologic characteristics of their lesions.