Facial seborrheic dermatitis is common in HIV-positive patients, and the presence of facial lesions can affect quality of life. The management and control of lesions can be frustrating for both physicians and patients. In this pilot clinical study, we clinically evaluated the effectiveness of a topical non-steroidal cream in treating mild to moderate facial seborrheic dermatitis in 20 HIV-positive patients. The patients applied a twice-a-day topical cream containing zinc PCA, piroctone olamine, hydroxyphenyl propamidobenzoic acid, biosaccharide gum-2, and stearyl glycyrrhetinate for 12 weeks with no topical or oral antifungal or corticosteroid treatment. Signs and symptoms and tolerance were assessed before, during, and at the end of treatment. All of the patients showed clinical improvement after 4 and 12 weeks of treatment. None of the patients had no response to treatment, and no adverse effects were reported. No rescue therapy with corticosteroids was needed. The patients reported a very noticeable improvement in their skin which contributed to high compliance with the protocol requirement.