Middle ear adenoma (MEA) is a distinctive, rare entity that appears to be derived from the lining epithelium of the middle ear mucosa. We report four cases of MEA displaying the typical histologic growth pattern. Two distinct tumor cell immunophenotypes were identified in all cases; the first type exhibited positivity with anti-epithelial membrane antigen and anti-keratin antibodies, and the second type showed immunoreactivity with anti-keratin, anti-vimentin, and anti-neuron-specific enolase antibodies. Ultrastructural studies revealed bidirectional mucinous and neuroendocrine differentiation, demonstrated by the presence of two distinct cell types containing apically located mucous granules and basally concentrated neuroendocrine granules, respectively. The presence of neuroendocrine differentiation was supported by the immunohistochemical detection of vasoactive intestinal polypeptide in the tumor cells in one case and neuron-specific enolase in three cases. These findings suggest that the potential for mixed mucinous/neuroendocrine differentiation described in other endodermally derived tumors also exists in middle ear mucosa. We also believe that the rare lesions diagnosed as primary carcinoid tumors of the middle ear might in fact be MEA with predominant or only neuroendocrine differentiation. The clinical course of our four cases and our review of the pertinent literature confirm the benign nature of MEA and indicate that these tumors should be treated by complete local excision without additional therapy.