Psoriasis is a chronic, immune-related disorder; inflammation, higher rate of epidermal proliferation, and angiogenesis are the main pathognomonic features. Cluster of differentiation 93 (CD93), an angiogenic element, plays a role in cell adhesion regulation and has a putative function in inflammation. To assess CD93 immunohistochemical expression in psoriatic skin and the association of CD93 single nucleotide polymorphisms (SNPs) rs2749817 to disease pathogenesis and severity. This case-control study was done on 50 patients with psoriasis vulgaris beside 50 age- and sex-matched healthy controls. Assessment of psoriasis severity was done by Psoriasis Area and Severity Index (PASI) score. 3mm punch skin biopsies were taken from every participant, and hematoxylin and eosin staining and immunohistochemical staining for CD93 antibody were done. Assessment of CD93 rs2749817 gene polymorphism by the TaqMan allelic discrimination assay technique (real-time PCR) was done. Immunohistochemical expression of CD93 showed membrano-cytoplasmic localization in both endothelial and inflammatory cells of cases and controls with significant more positivity in dermal endothelial and inflammatory cells of cases than controls (p=0.001 and 0.014 respectively). Strong intensity was present in 18 of cases endothelial cells and 24 inflammatory cells with absence in controls (p= 0.001 for both) with significantly higher H-score and higher percent of positive cells (p = 0.001 for both). The TC genotype was lower in patients compared to control (p-value=0.006) and CC genotype which was present only in cases (p-value=0.021). Cluster of differentiation 93 has an essential role in psoriasis and an encouraging future therapy for psoriasis.