A number of factors contribute to the pathogenesis of contact dermatitis (CD), including CD44. Previous research on an animal model has shown that CD44 could contribute to directing inflammatory cells into skin lesions during development of an inflammation present in allergic and irritant CD. Therefore, we have researched the expression of CD44 in patients with CD and compared the results with the disease severity of affected patients. Our research involves 50 patients with allergic CD and 50 patients with irritant CD. Patients of both groups have undergone biopsies of skin lesions and a patch test to contact allergens and were subsequently observed for a year, after which a questionnaire was performed and enquired about disease severity and accompanying issues. The samples collected during skin biopsies of patients with CD were compared to samples acquired from patients suffering from psoriasis vulgaris and a control group of samples of healthy skin (acquired by excising tissues surrounding the nevi). In all researched groups, the expression of CD44 was determined by immunohistochemical analysis using an optical microscope, after which the results were visualised semiquantitatively (by determining the percentage of immunoreactive cells in the epidermis, dermis, and lymphocytes). The results have shown statistically-significant differences between the researched groups (P<0.001) and the highest expression of CD44 in irritant CD, followed by allergic CD, psoriasis, and finally, the control group. Comparing disease severity (of allergic and irritant CD) with the expression of CD44 (in the epidermis, dermis, and lymphocytes of patients’ skin samples) has not shown a statistically-significant difference between the two groups. However, patients suffering from allergic CD have reported a higher severity of symptoms compared to those suffering from irritant CD (P<0.001). The main causes of this are greater areas of affected skin (P=0.006), more frequent systemic corticosteroid treatments (P=0.026), exposure to allergens (P<0.001), and greater impairment of patients in everyday activities (P=0.001). Significantly elevated expression of CD44 in irritant CD might be related to the function of CD44 in maintaining and preserving a skin barrier in affected patients.The mentioned problematics demand further research into disease pathogenesis and discovering new treatment options to improve patients’ quality of life and enable them to carry out everyday tasks.