The distribution of α v β 6 integrin was examined in oral leukoplakia, lichen planus and squamous cell carcinomas using immunohistochemistry. Controls included oral mucosal wounds, chronically inflamed and normal oral mucosa. Integrins β 1, β 3, β 4, β 5, fibronectin and tenascin were also studied. The integrin α v β 6 was highly expressed throughout the whole lesion of 90% of the squamous cell carcinomas but was not present in any of the normal specimens. α v β 6 integrin was also expressed in 41% of the leukoplakia specimens, and 85% of the lichen planus samples, but in none of the tissues with inflammatory hyperplasia or chronic inflammation. The expression of β1 integrins was localized in the basal layer, and that of the β 4 at the cell surface facing the basement membrane of all specimens. The integrins β 3 and β 5 were absent from all normal and leukoplakia specimens. Fibronectin and tenascin were present in the connective tissue underneath the epithelium of all the sections, and their expression was similar in both α v β 6-positive and α v β 6-negative tissues. A group of 28 leukoplakia patients were followed 1–4 years after first diagnosis. In this group, initially α v β 6 integrin-positive leukoplakia specimens had high tendency for disease progression while α v β 6-negative specimens did not progress. These results suggest that the expression of α v β 6 integrin could be associated in the malignant transformation of oral leukoplakias.© 2000 Cancer Research Campaign