AbstractBackgroundSeveral studies have challenged the traditional unipolar‐bipolar dichotomy in favor of a more dimensional approach.ObjectiveTo evaluate the differences in mood spectrum between patients with bipolar disorder (BD) and major depressive disorder (MDD) during a major depressive episode (MDE).MethodStudy participants were 145 patients with BD and 155 patients with MDD recruited at three University Medical Centers in Italy. All study subjects met Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for MDE and completed the Mood Spectrum‐Self‐Report‐Last Month questionnaire.ResultsPatients with BD endorsed more items in the mood manic/hypomanic and energy depressive subdomains of the MOODS‐SR questionnaire. Significant differences were also found for specific depressive and manic items, which were more frequently endorsed by patients with BD. A large number of patients with BD, but also a considerable number of patients with MDD, endorsed manic items during a depressive episode.ConclusionsThere are differences between BD and MDD in terms of the number and type of mood spectrum items that are endorsed during a MDE, which may help to identify patients with BD when a retrospective assessment of a history of mania or hypomania is not possible or not reliable. A high number of patients with BD and a considerable number of patients with MDD endorsed several items in the manic section of the mood, energy, and cognition domains, this confirming the centrality of mixed features in patients with mood disorders and the need for a unitary, dimensional, descriptive and dynamic approach to MDD and BD, such as the recently proposed ACE (Activity, Cognition, Energy) model.