Objective Schizophrenia may be the result of a failure of the normal lateralization process of the brain. However, whole-brain asymmetry has not been assessed up to date. Here we propose a novel measure of global brain asymmetry based on the Dice coefficient in order to quantify similarity between brain hemispheres. Method Global gray and white matter asymmetry was calculated from high-resolution T1 structural images acquired from 24 patients with schizophrenia and 26 healthy controls, age- and sex-matched. Some of the analyses were replicated in a much larger sample (n = 759) obtained from open-access online databases. Results Patients with schizophrenia had more global gray matter asymmetry than controls. Additionally, increased gray matter asymmetry was associated with avolition, whereas the inverse relationship was found for anxiety at a trend level. These analyses were replicated in a larger sample and confirmed previous results. Conclusion Our findings suggest that global gray matter asymmetry is related to the concept of developmental stability and is a useful indicator of perturbations during neurodevelopment.

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