Esthesioneuroblastomas (EN) exhibit problems in early diagnosis and therapy due to their localization at the frontal skull base. Analysis of six cases with EN (four male, two female; average age, 34.8 years) showed atypical initial symptoms, beginning as nasal bleeding, hyposmia and frontal headache. CT scans demonstrated hypo- to isodense tumors at the anterior skull base with extension to the sinuses and orbits. Five patients were operated on by an extranasal approach; one patient required orbital exenteration with later reconstructive surgery of the orbit by a microvascularly adapted forearm flap. One patient underwent a neurosurgical procedure first that was followed by chemotherapy and stereotactically guided radiation. One patient died 1 year after onset of therapy due to intracranial tumor. One patient developed lung metastasis 5 years after treatment. Four patients remain in clinical remission and receive regular follow-ups. Our analysis shows the guarded prognosis of EN despite multimodality therapy. This includes the problems of advanced disease with complications of surgery and radiation. All therapeutic procedures should be planned in collaboration with otolaryngologists, neurosurgeons and radiotherapists. New computer-aided and stereotactically guided radiation procedures can be helpful, especially in patients with extensive disease.