Oral erythroleukoplakia is characterized by severe dyskeratosis intermingled with multifocal erosive spots on the buccal mucosa, dorsal tongue, and lower lip, etc. A case of oral erythroleukoplakia was diagnosed among 83 cases of common oral leukoplakia since 1997. The pathological examination showed the typical features of leukoplakia with severe epithelial dysplasia, exhibiting dyskeratosis, acanthosis, and basal hyperplasia. The oral erythroleukoplakia was explored in comparison with a representative common oral leukoplakia by the immunohistochemical method using PCNA, β-catenin, EGFR, p53, TNFα, pAKT, and STAT3. Oral erythroleukoplakia showed strong positive reaction of PCNA, p53, EGFR, TNFα, pAKT1 and STAT3 in its spinous layer cells and these reactions were reduced in its basal layer cells, while common oral leukoplakia showed diffusely weak reaction of those proteins. Particularly, β-catenin was positive in the nuclei of some basal and spinous layer cells of oral erythroleukoplakia contrast to the common oral leukoplakia. These findings indicated that the present oral erythroleukoplakia was proliferative with the activation of β-catenin pathway, revealed the dysplastic changes of epithelium by the overexpression of EGFR, p53, and pAKT, and also produced inflammatory reaction through the activation of cytokine-dependent signalings of TNFα and STAT3. These data indicated that the present oral erythroleukoplakia might undergo the early stage of multi-step carcinogenesis via the overexpression of different oncoproteins, especially β-catenine, p53, pAKT, and STAT3.