In atopic dermatitis, microbial allergens may be pathogenetically significant. Apart from Staphyloccocus aureus, these are primarily lipophilic Malassezia yeasts. They are particularly involved in the pathogenesis of head and neck dermatitis (HND), a special form of atopic dermatitis, which is often difficult to treat. Fifty patients (21 men, 29 women) with moderate to severe HND of at least 6 months’ duration were included in a prospective double-blind study. All of them showed at least 10% involvement of the head-neck region. The severity of disease was evaluated by Investigator Global Assessment (IGA), Eczema Area and Severity Index (EASI) for the head-neck region and a pruritus score. IgE antibodies to Malassezia sympodialis and/or Malassezia furfur (at least CAP class 1) were a prerequisite for study enrollment. Either 1% ciclopiroxolamine cream (Batrafen; Aventis Pharma, Bad Soden, Germany) or the corresponding base cream were thinly applied to the affected areas twice daily for 28 days. Sixteen patients in the ciclopiroxolamine group and 13 patients in the placebo group completed the study. To assess the change in severity of atopic eczema, IGA differences between the individual measuring points were determined for all patients. There were significant differences in the IGA score change between the ciclopiroxolamine group and the placebo group, from t₃ to t₄, and over the total period. Similar, but not significant, changes were observed with the EASI score, in terms of affected skin area and itching. The present study is the first to examine the effect of antifungal single-drug therapy with a cream containing ciclopiroxolamine on the course of HND. The study medication was found to be significantly effective. To optimize this effect, suitable patients selected in terms of fungal load, specific IgE, prick test and particularly atopy patch test for Malassezia antigens could receive combined treatment with antimycotic-containing shampoos and/ or short-term systemic antimycotic therapy in severe cases.