Polychemotherapy or radiation frequently causes oral mucositis. Until now, only supportive options are available. Palifermin, a recombinant form of the human keratinocyte growth factor can avoid mucositis in patients treated with myeloablative polychemotherapy for allogeneic stem cell transplantation. Here, we present a patient treated with dose-intense conventional polychemotherapy suffering from severe mucositis leading to additional hospitalization. By using palifermin, the mucositis as well as further admissions were totally prevented. Furthermore, application in subsequent chemotherapy cycles demonstrated a safe and efficacious use. Hence, treatment with palifermin can prevent severe mucositis in a patient treated with dose-intense conventional polychemotherapy.