In the past, there have been many epidemiological and genetic studies of mood disorders, schizophrenia, and alcohol dependence, and in this study, the human serotonin 2A receptor (5-HTR2A) polymorphism was examined in 80 patients with mood disorders, 50 patients with schizophrenia and 41 patients with alcohol dependence. 5-HTR is related to affectivity, regulation, and pharmacologic effects of antidepressant, anti-anxiety and antipsychotic medications. The polymorphism in 5-HTR2A (102T/C, −1438 A/G) was identified by the polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP). The results suggest that 5-HTR2A (102T/C, −1438G/A) polymorphism might not be associated with susceptibility to schizophrenia or mood disorders, and it might not be a risk factor contributing to alcohol dependency. We found that the 102T/C polymorphism was in linkage disequilibrium with the −1438G/A polymorphism in psychosis (mood disorder, schizophrenia, and alcohol dependence) and in health controls. Further studies are needed to determine whether or not the novel serotonin receptor (5-HTR) polymorphism reflects the pathogenesis of schizophrenia, mood disorders, and alcohol dependence.