Integrins and cadherins are cell adhesion molecules suggested to play an important role in malignant progression and tumour differentiation. Our aim was to characterise the pattern of expression and the relations between integrin β1, β4, β6 and E‐cadherin and the different histopathological features important when judging tumour differentiation, using a well‐defined scoring system. Formalin‐fixed paraffin‐embedded pre‐irradiation biopsies from 85 patients with head and neck squamous cell carcinomas (HNSCC) were stained and evaluated for the expression of integrin β1, β4 and β6 and E‐cadherin. The integrins were upregulated in carcinomas compared to the adjacent mucosa and E‐cadherin was downregulated. However, differences were found within the tumour: Expression of E‐cadherin was lost and the three integrins were upregulated at the tumour borders, compared to central parts of the tumour biopsy. Expression of the integrins did not correlate with tumour or histopathological parameters, whereas expression of E‐cadherin was correlated with high degree of keratinisation, high nuclear maturation and few mitoses – factors that characterise well‐differentiated carcinomas ‐and E‐cadherin can therefore be considered as a marker of differentiation. Furthermore, loss of adhesion expressed by low E‐cadherin and integrin β4 correlated with the presence of nodal metastases at the time of diagnosis.