Background: The Diagnostic and Statistical Manual for Mental Disorders (5th edition) introduced the specifier “with Mixed Features” to the diagnosis of Major Depressive Episode to designate the presence of (hypo) manic symptoms as part of the clinical presentation. This change has led to renewed attention on the operational definition, diagnosis, and treatment of Mixed Depression. Objective: To investigate the diagnostic and therapeutic approaches towards Mixed Depression among a representative sample of Italian psychiatrists. Methods: Between March and April 2021, 342 psychiatrists working in Italian adult mental health services were invited to participate in an anonymous online survey comprising 32 questions designed to investigate clinical and psychopathological approaches regarding the management of mixed depression in daily psychiatric practice. Results: 83.74% of participants reported having performed a diagnosis of mixed depression in the last five years, with the majority of respondents affirming that they had not used any diagnostic tool. Only 7,5% of the surveyed psychiatrists considered the DSM-5 criteria to be fully adequate in the description of this clinical entity. The most used pharmacological approach was combined therapy, in particular antipsychotics plus mood stabilizers. For monotherapy, the preferred drugs were Valproate and Quetiapine. Regarding the conceptualization of mood disorders, 199 of the participants chose the Kraepelinian unitary spectrum view; meanwhile, 101 expressed their preference for the binary model. Conclusion: Our results suggest a prominent position of mixed depression in the context of mood disorders. Univocal operational criteria and additional research on pharmacological treatment are also needed to ensure the correct recognition and management of mixed depression.