Psoriasis vulgaris, a common inflammatory skin disorder, is known to be associated with the HLA-Cw*06 allele. It has been recently suggested by microsatellite mapping that a real susceptible gene for psoriasis resides in the approximately 100-kb genomic region telomeric of the HLA-C gene. In this respect, the corneodesmosin (CDSN) gene 160-kb telomeric of HLA-C is a strong candidate because of its location and its functional role in corneocyte cohesion and desquamation. In fact, a significant association between CDSN polymorphism and psoriasis was recently recognized in Caucasian populations. However, this association has not been replicated in other studies, being still controversial. In this study, we investigated the genetic polymorphism of the CDSN gene in 139 psoriasis patients and 144 healthy controls in the North-eastern Thai population. By direct sequencing technique, a total of 28 polymorphic sites were found, consisting of 26 single nucleotide polymorphisms (SNPs) and two indels (insertion/deletion). Among them, six SNPs have not been previously reported. Through this analysis, as many as 28 different SNP/indel haplotypes within the CDSN gene were identified. Seven SNPs and one indel, namely 9C, 614 A, 722T, 971T, 1215G, 1243C, 1331G and 1606AAG (deletion), revealed significant deviation in the allelic frequencies of the patients from those of the healthy controls. However, none of them are likely to be responsible for controlling the susceptibility of psoriasis, but these associations can be explained by a linkage disequilibrium to a real pathogenic allele of a nearby gene. Further, the large variations between the CDSN SNP/indel haplotypes and the psoriatic major histocompatibility complex (MHC) haplotypes also make it unlikely that CDSN is a major psoriasis-susceptible gene.