Different types of symptomatic trigeminal autonomic cephalalgias (TACs) have been reported in patients with pituitary adenoma. We investigated the significance of the presence of cranial autonomic symptoms (CAS) in patients with pituitary adenoma presenting with headaches. The records of patients with pituitary adenoma from 1998 to 2004 in our headache clinic were reviewed including headache profile, presence or absence of CAS, and the characteristics of the pituitary adenoma. CAS were ascertained if one or more autonomic symptoms defined for the diagnosis of TACs in the International Classification of Headache Disorders, 2nd edition (ICHD-2) was identified. Thirty-three patients (24F/9M) with pituitary adenoma presenting with headache were recruited for this study: 18 with CAS (55%) and 15 without. Chronic migraine was the most common headache phenotype (n=16, 48%). Three patients were diagnosed as hemicrania continua-like and three, cluster headache-like. In the group with CAS (CAS+), the sides of the tumor were significantly concordant with the sides of headaches (kappa=0.58, p<0.001) and those of CAS (kappa=0.67, p<0.001). However, this relationship was not demonstrated in those without CAS (CAS-) (kappa=0.07, p=0.61). Compared with the patients in the CAS- group, the patients in the CAS+ group had higher frequencies of macroadenoma (78% vs. 40%, p=0.027) and acromegaly (50% vs. 7%, p=0.009). The presence and absence of CAS in pituitary adenoma-associated headache were associated with different characteristics of the underlying pituitary adenomas including side concordance and incidence of acromegaly and macroadenoma. The pathogeneses for headache might differ between these two groups.