The objective of the present study was to test the association between Borderline Personality Disorder (BPD) and the cathecolamine-O-methyl-transferase (COMT) low-activity (Met158) single nucleotide polymorphism (SNP). In this case-control study, DNA was obtained from venous blood of 19 BPD patients and 36 healthy subjects. COMT-Val158Met single-nucleotide polymorphism was genotyped by predesigned SNP assay. The COMT Met158 allele was over-represented in patients with BPD in comparison to normal subjects (68.4% vs 44.4%, respectively; Fisher exact test, p = .02). In terms of genotype, the Met158Met subjects were more frequent in patients versus controls (47.4% vs 22.2%, respectively), whereas the high-activity genotype Val158Val was under-represented (10.5% vs 33.3%, respectively). The allele encoding for the COMT with low enzymatic efficiency was found to be over-represented in BPD, possibly resulting in excessive synaptic dopaminergic activity and ultimately affecting externalizing behaviours, such as impulsivity and aggressiveness.