Previous genetic studies showing an association between hypnotizability and the Catechol-O-Methil-Transferase (COMT) single nucleotide polymorphism (SNP) rs4680 (Val158Met) were inconsistent, as heterozygous subjects showed high mean score of hypnotizability in a few studies and intermediate score in others. In addition, the unique work based on the direct comparison between subjects with high (Highs) or low hypnotizability (Lows) was performed on a very small sample. In the present study, we used a selective genotyping approach to re-evaluate the association between hypnotizability and COMT, considering not only the Val158Met polymorphism, but also the closely located rs4818 SNP, in the context of a two-SNP haplotype analysis. An Italian sample of 53 Highs and 49 Lows (selected among 1043 subjects according to the Stanford Hypnotic Susceptibility Scale, form A) was genotyped by direct sequencing of the relevant portion of exon 4 of the gene. We did not find any evidence of association at the SNP, haplotype and diplotype levels. Whereas a positive association between hypnotizability and COMT would support the hypothesis that higher dopamine brain content accounts for the attentional characteristics of Highs, our results suggest that other factors, such as regional differences in catecholamines degradation, may be relevant in determining interindividual differences in hypnotizability.