Notch receptor–ligand interactions are critical for cell proliferation, differentiation and survival; however, the role of Notch signalling in psoriasis remains to be elucidated. Serum amyloid A (A‐SAA) is an acute‐phase protein with cytokine‐like properties, regulates cell survival pathways and is implicated in many inflammatory conditions. To examine the role of Notch‐1 signalling in the pathogenesis of psoriasis, Notch‐1, DLL‐4, Jagged‐1, Hrt‐1/Hrt‐2, A‐SAA, Factor VIII and vascular endothelial growth factor (VEGF) mRNA and/or protein expression in psoriasis skin biopsies, serum and dHMVEC were assessed by immunohistology, dual‐immunofluorescence, real‐time PCR, ELISA and Western blotting. A‐SAA‐induced angiogenesis and invasion in the presence of Notch‐1 siRNA was assessed by matrigel tube formation assays and Transwell invasion assay. Increased Notch‐1, its ligand DLL‐4 and Hrt‐1 expression were demonstrated in lesional skin compared with non‐lesional skin, with greatest expression observed in the dermal vasculature (P < 0.05). Dual‐immunofluorescent staining demonstrated co‐localization of Notch‐1 to endothelial cell marker Factor VIII. A significant increase in A‐SAA levels was demonstrated in psoriasis serum compared with healthy control serum (P < 0.05), and A‐SAA expression was higher in lesional skin compared with non‐lesional. In dHMVEC, A‐SAA significantly induced Jagged‐1, Hrt‐1 and VEGF mRNA expression (P < 0.05) and activated Notch‐1 IC indicative of transcriptional regulation. In contrast, A‐SAA significantly inhibited DLL‐4 mRNA expression (P < 0.05). Finally A‐SAA‐induced angiogenesis and invasion were inhibited by Notch‐1 siRNA (P < 0.05). Notch receptor–ligand interactions mediate vascular dysfunction in psoriasis and may represent a potential therapeutic target.