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Cholesteatoma is a non-neoplastic, keratinized squamous epithelial lesion that affects the temporal bone. The middle ear is the most frequent, while the isolated cholesteatoma of the mastoid is rare. The aim of this study was to describe a rare case of isolated mastoid cholesteatoma with no involvement of aditus ad antrum and middle ear including a literature review of the topic. This case report describes the case of a 58 years old female with a cholesteatoma isolated in the mastoid region, evidenced by imaging (computer tomography and magnetic resonance). A mastoidectomy was performed: mastoid process was completely involved, but antrum was not reached. Moreover, it reached the soft tissue of stylomastoid foramen as well as the posterior belly of the digastric muscle. In the literature few articles described cases of cholesteatoma isolated in the mastoid region. Research was conducted using PubMed and reference list and there were considered only reports about cholesteatoma exclusively located in the mastoid process without involvement of antrum or middle ear. Fourteen articles were included in this review, with a total number of 23 cases of cholesteatoma isolated in the mastoid region. All papers analyzed reported the cases of isolated mastoid cholesteatoma that presented a congenital origin. Its diagnosis is difficult, therefore, imaging evaluation is mandatory and surgery is the treatment of choice. Mastoid cholesteatomas without involvement of aditus ad antrum and middle ear are rare and only 23 cases are reported in literature. Our case is in line with all clinical and diagnostic features of this rare disease, but it is the only one that evidenced an exposure of the soft tissue of stylomastoid foramen as well as the posterior belly of the digastric muscle. The treatment of choice was the surgical one, avoiding damaging of important anatomo-functional structure.