OBJECT: Headache is the most common symptom of both primary and metastatic brain tumor, and is generally considered the primary symptom in patients with large pituitary adenomas. However, patients with small pituitary adenomas rarely complain of intractable headache, and neurosurgeons are unsure whether such small adenomas actually contribute to headache. If conventional medical treatments for headache prove ineffective, surgical removal of the adenoma can be considered as an alternative management strategy. METHODS: We conducted a retrospective review of 180 patients who underwent transsphenoidal surgery (TSS) for pituitary adenomas at Kanazawa University Hospital between 2006 and 2014. Patients with acute phase intratumoral hemorrhage were excluded. We identified nine patients with intractable headache as the chief complaint associated with small pituitary adenoma (diameters 15.8 ± 2.6 mm, 11-20 mm), non-functioning in eight, and prolactin-secreting in one. The preoperative neuroradiological studies and headache characteristics were assessed retrospectively, and the intrasellar pressure evaluation was performed during TSS in the last seven patients. RESULTS: All nine patients had complete or substantial resolution of their formerly intractable headache after TSS. Headaches consisted of ocular pain ipsilateral to the adenoma localization within the sella in four cases and bifrontal headache in five. Magnetic resonance imaging of these patients revealed small diaphragmatic foramen, which were so narrow that only the pituitary stalk could pass. Computed tomography scans showed ossification beneath the sellar floor in the sphenoid sinus, presellar type in six cases, and choncal type in three. The adenomas included cysts in seven cases. There was no cavernous sinus invasion. Intrasellar pressure measurements averaged 41.5 ± 8.5 mmHg, range 34-59, significantly higher than in control patients without headache (n = 12), namely 22.2 ± 10.6 mmHg (16-30). CONCLUSION: In this study, the authors demonstrated the validity of TSS in the treatment of intractable headache associated with pituitary adenoma. The presence of ocular pain, especially ipsilateral to the adenoma, integrity of the diaphragm sella, and ossification in the sphenoid sinus, cyst or hemorrhage and the absence of cavernous sinus invasion were the indications for TSS for patients complaining of intractable headache and having pituitary adenomas.