Aims: This study aims to test for possible associations between the gene coding for the 5-HT2C receptor and antipsychotic-induced weight gain. Materials & methods: Four HTR2C polymorphisms (rs498207, C-759T, G-697C and Ser23Cys) were investigated in our sample of 205 chronic schizophrenia patients. Results: Significant over-representation of the C–G–Cys23 haplotype in patients with weight gain (OR: 1.93; 95% CI: 1.04–3.56; p = 0.0015) was found. Similarly, haplotype analyses of percentage weight change were also significant (p = 0.029) for the C–G–Cys23 haplotype associated with the highest average percent weight gain. Observations in the polymorphisms are consistent with previous studies. An updated meta-analysis of nine previous studies plus our current sample suggest that the -759C allele is associated with antipsychotic-induced weight gain. Conclusion: Additional studies, including the resequencing of the region surrounding the HTR2C promoter, and functional studies of the promoter polymorphisms, may elucidate the mechanism underlying this genetic association.