This chapter offers some speculations on the neuropathological substrate that gives rise to both schizotypal personality disorder (SPD) and schizophrenia. It examines the developmental phenomenology of schizophrenia and SPD. Research on the biological offspring of schizophrenic patients indicates that those who are diagnosed with SPD in adulthood showed neuromotor abnormalities in infancy. A comprehensive neurodevelopmental model of any disorder must account for its changing manifestations of dysfunction across the life course. In case of schizophrenia, the evidence of neuromotor dysfunction in particular, dyskinesia is most pronounced early and late in the life course, and florid psychotic symptoms that are most pronounced in early adulthood. Differences between SPD and schizophrenia may be revealed by positron emission tomography (PET) in studies of receptor activity in the limbic striatum. Postmortem investigations are performed to identify differences between SPD and schizophrenia in myelination and cytoarchitectonics of the limbic circuitry.