The aim of the present study was to investigate the clinical usefulness of an observational tool--the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS)--in the diagnosis of disruptive behavior disorders (DBD) and attention deficit/hyperactivity disorder (ADHD) in preschoolers. We hypothesized that the DB-DOS may help support the presumption of a diagnosis generated by the information from parents and teachers (or other caregivers). Participants were referred preschool children with externalizing behavioral problems (N = 193; 83% male) and typically developing children (N = 58; 71% male). In view of the clinical validity study each child was given a diagnosis of either DBD (N = 40), or ADHD (N = 54) or comorbid (DBD + ADHD; N = 66) based on best-estimate diagnosis. The DB-DOS demonstrated good interrater and test-retest reliability for DBD and ADHD symptom scores. Confirmatory factor analysis demonstrated an excellent fit of the DB-DOS multidomain model of DBD symptom scores and a satisfactory fit of ADHD symptom scores. The DB-DOS demonstrated good convergent validity, moderate divergent validity, and good clinical validity on a diagnostic group level for DBD and ADHD symptom scores. The Receiver Operating Characteristic curve analyses revealed that for DBD the sensitivity and specificity are moderate and for ADHD good to excellent. The presumption of a diagnosis based on information from parents, teachers, and cognitive assessment was supported by the DB-DOS in 60% for DBD and 75% for ADHD. The DB-DOS can be used to help support a presumption of a DBD and/or ADHD diagnosis in preschool children.