Human induced pluripotent stem cells (hiPSC) provide an attractive tool to study disease mechanisms ofneurodevelopmental disorders such as schizophrenia. A pertinent problem is the development of hiPSC-based assaysto discriminate schizophrenia (SZ) from autism spectrum disorder (ASD) models. Healthy control individuals as well aspatients with SZ and ASD were examined by a panel of diagnostic tests. Subsequently, skin biopsies were taken for thegeneration, differentiation, and testing of hiPSC-derived neurons from all individuals. SZ and ASD neurons share areduced capacity for cortical differentiation as shown by quantitative analysis of the synaptic marker PSD95 andneurite outgrowth. By contrast, pattern analysis of calcium signals turned out to discriminate among healthy control,schizophrenia, and autism samples. Schizophrenia neurons displayed decreased peak frequency accompanied byincreased peak areas, while autism neurons showed a slight decrease in peak amplitudes. For further analysis of theschizophrenia phenotype, transcriptome analyses revealed a clear discrimination among schizophrenia, autism, andhealthy controls based on differentially expressed genes. However, considerable differences were still evident amongschizophrenia patients under inspection. For one individual with schizophrenia, expression analysis revealedderegulation of genes associated with the major histocompatibility complex class II (MHC class II) presentationpathway. Interestingly, antipsychotic treatment of healthy control neurons also increased MHC class II expression. Inconclusion, transcriptome analysis combined with pattern analysis of calcium signals appeared as a tool todiscriminate between SZ and ASD phenotypes in vitro.