Cyclin E plays a pivotal role in the regulation of G₁-S transition and relates to malignant transformation of the cells. However, the clinical significance of cyclin E expression in patients with non-small cell lung cancer remains unknown. We examined the expression of cyclin E in 242 resected non-small cell lung cancer in pathological stages I–IIIa and analyzed its relation to clinicopathological factors. Cylin E overexpressions were observed frequently in deeply invasive tumors. Multivariate analysis revealed that complete resection, pathological stage, and cyclin E expression were independent prognostic indicators. When cyclin E and proliferating cell nuclear antigen are combined, the cases negative for both had a significantly better prognosis than the other cases. We concluded that cyclin E overexpression relates to deeply invasive tumors and is correlated with poor prognosis. New therapeutic options may be provided by combination of cyclin E expression and proliferating cell nuclear antigen overexpression.