AbstractSix patients with malignant head and neck tumors are shown to have required electron microscopy for accurate diagnosis. In all of these tumors, there were ultrastructural features of cytodifferentiation that were not discernible by light microscopy, such as neurosecretory granules, desmosomes, cytoplasmic processes, tonofibrils, and myofilaments. Electron microscopy is helpful in the differential diagnosis of tumors in general, but its effectiveness is particularly apparent in small‐cell “undifferentiated” tumors such as neuroblastoma, rhabdomyosarcoma, Ewing's sarcoma, undifferentiated squamous‐cell carcinoma of the lymphoepithelioma type, and malignant lymphoma. It has also been helpful in the identification of amelanotic melanoma and spindle‐cell