The aim of this study was to evaluate HSP27 expression in fetal, normal and inflamed oral mucosal epithelium and in oral premalignant epithelial lesions and in their ensuing invasive cancers. In developing human oral epithelia, immunoreactions for HSP27 were moderately observed in suprabasal keratinocytes of palate and tongue. Normal oral epithelium had an intense suprabasal positivity. In inflamed oral mucosa, HSP27 staining was stronger in basal and suprabasal keratinocytes than in normal epithelium. Most oral premalignant lesions showed no (5 cases, 29%) or low (8 cases, 46.4%) staining. In OSCC both low and high HSP27 levels of expression were observed. HSP27 immunolabelling was down-regulated in poorly differentiated areas and up-regulated in highly differentiated ones. These findings indicated that HSP27 expression seems to protect cells from apoptosis during inflammation, while the down-regulation in dysplasia could impair the protective mechanism against mutagenesis induced by environmental factors and thus enhancing the transformation of oral epithelial dysplasia into OSCCs.