The relationship between subclinical hypothyroidism and depression is still controversial. Our objective was to compare the prevalence of depressive symptoms and major depressive disorder in a population of patients affected by subclinical hypothyroidism and a control group without thyroid disease. The authors enrolled 123 consecutive outpatients affected by subclinical hypothyroidism undergoing follow-up at the endocrinology department of San Paolo Hospital in Milan and 123 controls without thyroid disease under the charge of general physicians.All patients and controls underwent an evaluation by means of a psychiatric interview; Hamilton Rating Scale for Depression (HAM-D); Montgomery-Asberg Depression Rating Scale (MADRS); and serum thyroid stimulating hormone, free T4, and free T3 levels. Patients were also screened for thyroid peroxidase antibodies and thyroglobulin antibodies. Patients affected by subclinical hypothyroidism had a prevalence of depressive symptoms of 63.4% at HAM-D and 64.2% at MADRS; 22 patients (17.9%) had a diagnosis of depressive episode (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria). The control group had a prevalence of depressive symptoms of 27.6% at HAM-D and 29.3% at MADRS, and only seven controls had a diagnosis of depressive episode. The prevalence of depressive symptoms between these two groups was statistically different. This study underlines a strong association between subclinical hypothyroidism and depressive symptoms, which could have some important diagnostic and therapeutic implications in the clinical practice.