Purpose: This case-control study was designed to determine whether adults who present to a primary care office with a chief complaint of headache have more reported symptoms of depression than adults presenting with other problems.Methods: Adult, English-speaking patients who presented to a primary care office with a chief complaint of headache were matched to adult patients of the same age and sex who presented with problems other than headache. All participants completed the PRIME-MD 9-item Patient Health Questionnaire as a screen for depression.Results: A total of 200 participants entered the study. The mean age of the participants was 43.8 years (range, 18 -87 years). Women constituted 84% of the participants. Of those patients who presented with headache, 32% had a likelihood of possible major depressive disorder compared with 12% in the patients presenting without headache.Conclusions: Almost one-third of adult patients who present to a primary care office with a complaint of headache report moderate symptoms of depression when screened compared with approximately 10% of patients presenting with a complaint other than headache. Given such a high prevalence of these symptoms, primary care physicians should screen all adult patients who present with headache for depression. It is estimated that more than 90% of adults experience at least one headache each year. Although the majority of those adults do not seek medical attention for this problem, headache is one of the top reasons for people to seek outpatient medical care. Depression is also a common disorder seen in the outpatient setting. In primary care, anywhere from 5% to 10% of outpatients have major depression.