Major Depressive Episod (MDE) delimits a wide range of heterogeneous disorders. Nowadays, both for research and for therapeutic aims, precise characteristization of MDE subtypes are needed, different subtypes of MDE requiring individualized short, long-term and preventive treatments. As patients mainly seek for physician help during the full-blown depressive phase, we focused our study on patients presenting a major depression as the index episode. In order to attempt to isolate subtypes of the disorder relatively to the mood spectrum disease and to obtain a better clinical characterization of each, we have considered the role of soft indicators of bipolarity or of milder mood disregulations in distinguishing among subtypes of MDE; special attention was devoted to detect spontaneous or drug-induced hypomania, as well as to assess the hyperthymic or cyclothymic temperament, and family history for mood disorders. Data on prior course, characteristics of index episode, and familial aggregation of patients with Bipolar II Disorder support the autonomy of this condition. Differently from our previous analyses we considered Bipolar II with hypomanic episodes separately from U-HT unipolar with only hyperthymic temperament. The comparison between these two subgroups showed a higher percentage of males in the hyperthymics, longer duration of illness and a greater number of depressive episodes and hospitalizations in bipolar II with hypomania. Data from our analyses are exposed and discussed.