The relationship between psychiatric symptoms and thyroid function has been well known and studied since antiquity. The common view is that clinical hypothyroidism is associated with depressive symptoms, whereas the psychiatric manifestations of hyperthyroidism are agitation, emotional lability, hyperexcitability, occasionally accompanied by angry outbursts, and euphoria. The case here reported overturns this conventional medical knowledge. A 73-year-old Italian woman experienced a severe major depressive episode with psychotic and melancholic features during laboratory thyrotoxicosis. No classical clinical signs and symptoms of thyrotoxicosis were present. Psychiatric symptoms improved together with the resolution of the hyperthyroid state. Historically, different cases of so-called ‘apathetic hyperthyroidism’ have been described. Recent neuroimaging and animal studies provided possible neurobiological explanations, showing how the excess thyroid hormones could affect brain structures involved in the regulation of mood, leading to depression. A direct link between hyperthyroidism and depression seems to be likely. This insight may be relevant in facilitating early diagnosis of thyroid disease and the planning of therapeutic strategies.