To examine the behavioral and emotional difficulties of 73 children and adolescents with Prader-Willi Syndrome (PWS), mental retardation-only, and dual diagnosis (i.e., mental retardation and psychiatrically disordered) on the Devereux Scales of Mental Disorders (DSMD: Naglieri, LeBuffe, & Pfeiffer, "Devereux Scales of Mental Disorders" (DSMD) San Antonio, TX: PsychCorp 1994). Multivariate analyses and "Italic" greater than d-ratios were computed to assess the statistical and clinically meaningful differences between pairs of samples. The PWS sample exhibited statistically significant higher levels of psychopathology than the mentally-retarded-only sample on the Total, Externalizing, Internalizing, Attention/Delinquency, Conduct, Anxiety, and Acute Problems Scales. When compared to the dually-diagnosed sample, children with PWS Syndrome had comparable levels of psychopathology, but lower levels of depression. Results revealed that PWS represents a highly unique and complex psychological disorder with multiple areas of disturbances.