Background: Although manic or hypomanic episodes define bipolar disorder (BD), most patients show a predominance of depressive symptomatology, often associated with delayed or disregarded BD diagnosis. The Hypomania Checklist-32 (HCL-32) has therefore been developed and tested internationally to facilitate BD recognition. Sampling andMethods: Five hundred seventy-one (563 eligible) patients diagnosed with a major depressive episode according to DSM-IV criteria were consecutively enrolled in a cross-sectional, multicenter, observational study (Come To Me). Lifetime manic or hypomanic features were assessed by the HCL-32, and severity of depressive and anxious symptomatology was assessed using the Zung’s self-report questionnaires for depression and anxiety. Results: Among the patients diagnosed with BD (n = 119), either type I or type II, the occurrence of (hypo)manic symptoms was significantly higher compared to major depressive disorder (MDD) symptoms according to HCL-32 total and subscale scores obtained using a score of 14, which ensured an optimal discrimination between BD and MDD with a sensitivity of 0.85 and a specificity of 0.78. Conclusions: Although some false positives might occur, the HCL-32 was confirmed to be a useful instrument in the detection of past hypomania in MDD patients, finally contributing to proper therapeutic choices.