Borderline personality disorder (BPD) is a serious illness that is frequently underdiagnosed. A previous psychometric analysis of the 9 BPD criteria in DSM-IV/DSM-5 found that the affective instability criterion functioned well as a screen for the disorder. A limitation of that initial study was that the performance of the BPD criteria was examined in a diagnostically heterogeneous sample, including those with a low likelihood of having BPD. The present study from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project examined the operating characteristics of the BPD criteria in patients with major depressive disorder (MDD) and bipolar disorder. From December 1995 to April 2014, 3,674 psychiatric outpatients were evaluated with a semistructured diagnostic interview for DSM-IV BPD. The operating characteristics of the BPD criteria were examined in 3 nonoverlapping groups of patients: those with a principal diagnosis of MDD, those with a principal diagnosis of bipolar disorder, and all remaining patients. The sensitivity and negative predictive value of the affective instability criterion were greater than 90% in patients with MDD, bipolar disorder, or other diagnoses. Of the 9 BPD criteria, the affective instability criterion achieved the highest sensitivity and negative predictive value in all 3 diagnostic groups. Despite the phenomenological overlap between BPD and mood disorders, inquiry about affective instability functions well as a clinically useful screen for BPD in patients with MDD and bipolar disorder. In patients presenting for the treatment of MDD or bipolar disorder, clinicians should screen for BPD in the same way that they screen for other comorbid psychiatric disorders-by inquiring about a single feature of the disorder (ie, affective instability), the presence of which captures almost all patients with the disorder and the absence of which rules out the disorder.