The pathologic and clinical findings in cases of desmoplastic melanoma of the head and neck seen at the Mayo Clinic in Rochester, Minnesota, during the past 20 years were analyzed. The nine cases acceptable for study included six usual and three neurotropic variants as defined by light microscopic criteria. Immunopathologic studies of all cases using S-100 protein and desmin, and electron microscopy in four cases, were unsuccessful in distinguishing between the two subtypes. Clinical behavior was aggressive regardless of histologic subtype. Extensive surgical treatment when the diagnosis is made is advocated. The combination of the rarity and the subtle histologic features of desmoplastic melanoma continues to make the correct diagnosis of this entity a challenge for the clinician and pathologist.