An immunohistochemical study was performed of changes in the expression of adhesion molecule CD44 in 32 adjacent non-tumour epithelia (ANTE) to lingual carcinomas and in the tumour tissue, using anti-CD44 monoclonal antibody DF1485. The aim was to evaluate the importance of these changes as an early event in lingual carcinogenesis. The ANTE was histologically normal in 22 cases (68.8%) and presented epithelial dysplasia in 10 (32.2%). Three cases of normal and dysplastic ANTE, respectively, were CD44- (9.4%). Negative CD44 expression was significantly more frequent in tumours with lower percentages of CD44+ cancer cells, both in normal (P=0.014) and dysplastic (P=0.033) ANTE. The expression in normal ANTE was also significantly associated with clinical stage (P=0.040) and presence of extracapsular nodal spread (P=0.013). Therefore, loss of CD44 expression in ANTE can be considered an early event in lingual carcinogenesis and a marker of major alterations of CD44 expression in the derived tumour tissue.