Major depression can present with atypical symptomatology and as a consequence, delay can occur in passing through the relevant algorithm for biological treatment. The case of a 62-year old female is presented who eventually was diagnosed with a major depressive episode, with psychotic features. The atypical presentation led to persistent diagnostic uncertainty both during outpatient treatment in several mental health care institutions and during inpatient observation. As a consequence, proceeding to the next step of the algorithm for biological treatment for major depression was delayed. Factors involved in this diagnostic uncertainty are discussed.