Autofluorescence bronchoscopy (AFB) has been shown to be sensitive to detect preneoplastic lesions in central lung airways system. In early stages of carcinogenesis, up-regulation of cyclooxygenase (COX)-2, Ki67 and/or increased angiogenesis may play a role by promoting the proliferation of tumoral cells and their resistance to apoptosis, as well as angiogenesis, tumor cell invasion and setting up of the metastatic process. The present study compared the expression of proliferative (COX-2, Ki67 and PCNA) and angiogenic markers (CD34 and NG2) between preneoplastic bronchial squamous dysplasia lesions and invasive squamous cell carcinoma. Biopsies obtained during AFB [preneoplastic lesions: low-grade (lesions up to moderate dysplasia), n=13; high-grade lesions (severe dysplasia), n=12] and surgical specimens (resections of bronchogenic carcinoma, n=11) were stained with COX-2, Ki67, PCNA, CD34 and NG2 monoclonal antibodies. Microvessel density (MVD) was analysed based on anti-CD34 immunostaining. Lesions were positive for COX-2 in 12 out of 25 preneoplastic lesions, and in 10 out of 11 invasive carcinomas (p=0.025). In preneoplastic lesions, the mean percentage of Ki67 positive cells was lower compared to invasive carcinomas (37.4+/-5.8 versus 58.6+/-8.4%, p=0.043). In addition, significant differences in MVD were observed between preneoplastic and NSCLC specimen [35.3 (25.9, 61.9) versus 22.1 (20.1, 32.6), p=0.016]. No differences were observed in the mean percentage of PCNA or NG2 positive cells between preneoplastic lesions and invasive carcinomas. Findings of the present study indicate that increases in COX-2 and Ki67 expression may be associated with the development of bronchogenic carcinomas and possibly with acquisition of an invasive phenotype. In contrast, increased CD34 expression in preneoplastic lesions suggests that increased MVD may represent an early marker of lung carcinogenesis.