AIM: To examine tumour samples immunohistochemically for MUC1 (episialin), epidermal growth factor receptor (EGFR), and c-erbB-2, since the disruption of the cell-cell adhesion system by MUC1 and the c-erbB oncoprotein family is known to be important in the development of metastasis in human cancers. METHODS: 93 tumour samples from patients with early stage non-small cell lung cancer treated with surgery alone were examined for episialin, EGFR, and c-erbB-2. RESULTS: Episialin depolarised expression did not correlate with any of the histopathological variables examined (T,N stage, grade, histology, Ki67 proliferation index). No correlation was observed between episialin and EGFR or c-erbB-2 expression. Survival analysis showed that episialin depolarised expression correlated with poor prognosis (p = 0.003), especially in squamous cell cases (p = 0.0003). Episialin expression defined a group of patients with poor prognosis in the node positive category (p = 0.003). In multivariate analysis episialin was the most significant independent prognostic factor (p = 0.007), followed by N stage (p = 0.04). CONCLUSIONS: Depolarised expression of episialin is associated with poor outcome in early stage non-small cell lung cancer. Despite the similar activity on the cadherin cell-cell adhesion system, the expression of episialin and c-erbB oncoproteins is likely to be activated within different pathogenic pathways.