<b><i>Background:</i></b> Lung cancer is one of the commonest malignancies with a worldwide incidence of 1.6 million cases each year. Although the main aetiological factor has been identified (cigarette smoking), the progression of lung cancer from early changes such as dysplasia through to cancer is still not fully understood. Furthermore, current research techniques are reliant on obtaining tissue biopsies, a process that alters the natural history of the very process under investigation. Hence, there is a need for developing optical biopsy techniques. <b><i>Objectives:</i></b> To prospectively evaluate the feasibility of endocytoscopy and confocal endomicroscopy in the detection of malignant and pre-malignant changes in the airways. <b><i>Methods:</i></b> Findings with endocytoscopy and endomicroscopy were compared with conventional biopsies obtained from the same areas in 25 patients undergoing bronchoscopy for evaluation of endobronchial abnormalities and in 5 healthy control subjects. <b><i>Results:</i></b> Endocytoscopy was technically more difficult, and interpretable images were only obtained in 21 of the patients evaluated, and hence, complete information including histopathological information was available in 21 patients. Endocytoscopy appeared to correlate with the histopathological findings on tissue biopsy, and was able to distinguish normal epithelium from dysplasia and carcinoma. Confocal endomicroscopy was a more reliable technique with adequate visual information obtained in all patients examined but was unable to distinguish between dysplasia and carcinoma. <b><i>Conclusion:</i></b> This feasibility study suggests that endocytoscopy may have the potential to fulfil the role of optical biopsy in the evaluation of the pathogenesis of lung cancer.