Objective: The schizophrenia and other non-affective disorders categories listed in the DSM-IV, are currently under revision for the development of the fifth edition. The aim of the present study is to demonstrate the validity of these categories by investigating possible differences between diagnostic patient subgroups on various measures. Methods: 1064 patients with a diagnosis of non-affective psychosis (schizophrenia N = 731 (paranoid type 82%), schizoaffective N = 63, schizophreniform N = 120, psychosis not otherwise specified/brief psychotic disorder N = 150) participated in this study. Dependent variables were demographic and clinical characteristics, severity of psychopathology, premorbid and current functioning, and indicators of quality of life. Results: Within the diagnostic group of schizophrenia, no significant differences were observed between paranoid schizophrenia, disorganized, and undifferentiated schizophrenia. Patients with schizophrenia experienced more severe psychopathology and had poorer levels of current functioning compared to patients with psychosis not otherwise specified or brief psychotic disorder. Differences between schizophrenia and schizoaffective disorder were less clear. Conclusion: Our results do not support the validity of schizophrenia subtypes. Schizophrenia can be distinguished from brief psychotic disorder and psychotic disorder not otherwise specified. These findings may fuel the actual DSM-V discussion.