Apoptosis a known homeostatic regulator in normal epidermis, has been observed in various skin disease, but whether it is involved in the pathogenesis of cholesteatoma and aural malignancies is not known. In the present study, apoptosis in specimens of normal meatal skin (n=11), cholesteatoma (n=23), and squamous cell carcinoma (SqCC) (n=14) of the ear was investigated by morphological assessment and specific in situ labelling of fragmented DNA (Terminal deoxynucleotidyl transferase-mediated dUTP. Nick-End Labelling, TUNEL). Apoptotic cells showing perinuclear condensation and apoptotic bodies were observed by light microscopy of normal, cholesteatomatous and cancerous epithelium. TUNEL also elicited positive nuclear staining in apoptotic cells. In normal skin, TUNEL-positive cells were localized mainly in the granular layers, but were not so restricted in cholesteatoma, while in SqCC they were even more dispersed. In normal skin, the apoptotic index (AI) was low (l.59 ± 0.10 SEM), was increased in cholesteatomatous epithelium (2.09 ± 0.11), and was intermediate in SqCC (1.72 ± 0.14). By contrast, the mitotic index (MI) showed that epithelial cell proliferation had increased, from 0.19 ± 0.02 in normal skin, to 0.25 ± 0.01 in cholesteatoma and to 0.25 ± 0.02 in SqCC. Our findings indicate that apoptosis plays an important role in the epithelial homeostasis of normal aural skin, in cholesteatoma and in SqCC of the ear. A higher frequency of apoptosis is a reflection of the hyperproliferation of epithelial cells in cholesteatoma, while the reduced apoptosis rate in SqCC suggests that the malignant transformation of aural epithelium may be associated with inhibition of apoptosis.