The aim of this article is to generate hypotheses for the mechanism of pituitary adenoma headache. Patients and methods: Fifty-eight patients with pituitary adenoma were prospectively analysed for prevalence and manifestation of tumour headache. Intrapersonal and neoplasm-associated risk factors were assessed. Results: Twenty-four patients (41%) had tumour-attributed headache, seven had migraine-like, 11 tension-type headachelike headache, and three both. Cluster headache-like headache was found once, and two headaches remained unclassified. Tumour-attributed headache was associated with a positive history of headache (p=0.03; OR 3.4), nicotine abuse (p0.01; OR 4.7), intake of acute headache medication (p=0.04; OR 3.3), and a higher tumour proliferation indicated by a Ki67-labelling index (LI) 3% (p=0.02; OR 11.0). For patients with migraine-like tumour-attributed headache, risk factors were younger age (p=0.02), nicotine abuse (p0.01; OR 10.9), acute headache treatment (p0.01; OR 9.0), and Ki67-LI 3% (p=0.03; OR 14.1). For tension-type headache-like headache, the main risk factor was a positive history of tension-type headache (p=0.045; OR 5.6). Conclusion: Headache predisposition and local tumour effects might be important for the pathophysiology of pituitary adenoma headache and tumour headache in general.