In this case study, we report on a patient complaining of headache who, after CT and MRI, was found to have a neoplasia of the left sphenoid sinus. After a transnasal biopsy and histological examination, a prolactinoma was diagnosed. Based on this case, we discuss important aspects of tumor biology, diagnostic procedures, histology as well as differential diagnosis. Prolactinoma has to be considered as a differential diagnose in all sphenoid sinus neoplasias with close contact to the pituitary gland.