Introduction: Hyperprolactinemia is a common serious side effect of antipsychotic medications that are currently used in the treatment of patients with schizophrenia. Pharmacogenetic approaches offer the possibility of identifying patient-specific biomarkers for predicting the risk of this side effect. We investigated a possible relationship between variants (SNPs) in genes for cytochrome 2D6 (CYP2D6), dopamine-2 receptor (DRD2) and serotonin-2C receptor (HTR2C) and antipsychotic drug-induced hyperprolactinemia in patients with schizophrenia. Methods: Overall, 128 Russian patients with paranoid schizophrenia (61F/67M, aged 18-65 y) were included. Serum prolactin concentration was measured with ELISA. DNA analysis and genotyping of CYP2D6 (rs3892097), DRD2 (rs6275) and HTR2C (rs6318) genes was done with StepOnePlus Real-Time PCR System using TaqMan (R) SNP Genotyping Assays (Applied Biosystems, USA). Results: Our study showed an association of the CYP2D6 (rs3892097) and HTR2C (rs6318) gene polymorphism with hyperprolactinemia in patients with schizophrenia on the background of therapy. No associations were identified between the DRD2 (rs6275) gene polymorphism and the risk of antipsychotic-induced hyperprolactinemia in patients with schizophrenia. Conclusion: Our study confirms a contribution of genetic factors to the antipsychotic-induced hyperprolactinemia in patients with schizophrenia. Further studies are required to unravel the genetic predictors of antipsychotic-induced side effects and to develop the personalized treatment strategies for patients with schizophrenia.