A recent survey of head and neck cancer indicated a sharp difference in survival between cancer of the hypopharynx and cancers formed in other head and neck sites. We have analyzed tumor size relative to clinical stage and vascularization as possible causes for such a difference in a series of 21 patients with cancer of the laryngopharynx (11 glottic and 10 hypopharyngeal). We found that the volume of the smallest cancers of the larynx at stage 2 is significantly larger than the volume of the cancers of the hypopharynx at stage 4 (P < 0.05). Next, we have determined by immunohistochemistry and morphometry the microvessel density, microvessel perimeter, and vascular endothelial growth factor (VEGF) expression of laryngo-hypopharyngeal cancers. Analysis of these data indicates that there is no difference in vascularization and VEGF expression between these two tumor types. These data strongly suggest that the invasive but not the angiogenic phenotype of hypopharyngeal cancer cells could be responsible for the more aggressive biologic behavior of this head and neck cancer subtype.