Aims: To determine the contributions of mast cells (MC), eosinophil leucocytes (EL) and microvessel den-sity (MVD) in lip carcinogenesis, and to establish the relationships between these biomarkers and their possible prognostic value in lip squamous cell carci-noma (LSCC). Methods and results: Archived specimens of lip mucosa (n= 13), actinic cheilitis (n= 29) and LSCC (n= 29) were formalin-fixed, paraffin-embedded, sectioned and stained with toluidine blue and haematoxylin and eosin (H&E) in order to identify MC and EL and to measure their densities. Tumour angiogenesis was estimated by determining, with the use of CD31 antibody MVD in areas with the highest number of stained microvessels (‘hot spots’). Progressive increases of MC, EL and MVD were observed during lip tumour development. Correla-tion analysis revealed positive associations between the biomarkers during tumour progression. In LSCC sam-ples, significant associations were found between MVD values and metastatic disease. On multivariate analysis, MVD was a predictor of risk of cervical metastasis. Conclusions: The densities of MC, EL and microvessels increase during lip carcinogenesis, and for MC and EL this may be related to the stimulation of tumour angiogenesis. MVD could be a useful predictor of cervical metastasis in LSCC