A rare case of solitary plasmacytoma of the sphenoid sinus involving the pituitary fossa is reported. A 50-year-old woman with a history of diplopia and a mass in the sphenoid sinus and the sellar region, documented by computed tomography, was referred to our department with a presumed diagnosis of nonfunctioning pituitary adenoma. The clinical and biochemical characteristics were unrevealing, but magnetic resonance imaging examination demonstrated the extrapituitary origin of the lesion. The patient was operated on by the transsphenoidal approach, and the lesion was histologically diagnosed as a plasmacytoma. Review of the literature disclosed 11 previously described cases of myelomatous disease presenting clinically as a pituitary adenoma. Our case demonstrates that magnetic resonance imaging investigation may help in distinguishing the extrapituitary origin of a mass involving the pituitary fossa.