Introduction: It is our conviction that mood, anxiety and impulse-control dysregulation, lie at the psychopathological core of the Addictions. In this vision, we are confident that Heroin Use Disorder (HUD) has a specific psychopathology when compared with other mental disorders. Methods: We compared 972 HUD patients with 504 Major Depression (MD) patients on the basis of five SCL-90 dimensions that had previously been identified in HUD patients, with the purpose of estimating the magnitude of the differences, in terms of psychopathological symptoms. Results: Prominent psychopathological domains are more frequent in HUD patients, in particular, “worthlessness and being trapped”, “somaticsymptoms” and “sensitivity psychoticism”. The “violence-suicide” dimension is more frequent in MD patients, while the “panic anxiety” dimension fails to differentiate between the two groups. The prominent psychopathological groups are the most important factor in significantly differentiating between the two groups, when drawing comparisons on the basis of age, male gender and the severity of psychopathological symptoms. Conclusions: Our results suggest that the five found psychopathological dimensions seem to confirm the trait, instead of the state, nature of our proposed psychopathology of heroin addiction. In any case, the psychopathological symptoms of HUD and MD patients seem to differ quantitatively and qualitatively.