Spread of tumor to intracranial structures is an infrequent and late manifestation of head and neck cancers. We recently encountered six patients with a distinct clinical syndrome due to involvement of the cavernous sinus, which forms the basis of this report. This syndrome was a source of significant morbidity and mortality, with a mean survival of only 4 months. The diagnosis is often elusive, but is now made more commonly than previously. Whether this reflects increased incidence (due to alterations in the natural history of disease by therapy) or improved diagnosis (due to modern imaging modalities) is unknown. Cavernous sinus involvement may be the first evidence of distant disease in head and neck cancer. Although survival is poor, palliation is worthwhile. Awareness of this syndrome can lead to earlier diagnosis and alteration of treatment.