There were clinical and histological similarities among verrucous hyperplasia (VH), verrucous carcinoma (VC) and squamous cell carcinoma (SCC) of the oral cavity, especially, in those cases with borderline morphology. The aim of this study was to evaluate the differences among oral VH, VC and SCC by silver-binding nuclear organizer regions stain (AgNORs) and immunohistochemical staining for proliferating cell nuclear antigen (PCNA), type IV collagen and laminin. Thirty-one cases of VH, 32 cases of VC, and 66 cases of SCC were retrospectively retrieved from blocks of paraffin. The number of AgNORs in VH, VC and SCC were 5.21±0.30, 6.57±0.30 and 9.03±0.37per cell, respectively. As the degree of malignancy increased, the number of AgNORs significantly increased. Immunostaining showed that two to three layers of PCNA-positive cells were present in the peripheral area of the tumor nests of VC, but with a diffuse disseminated distribution in the tumor nests of SCCs. The positive rates of PCNA of every 100 cells on VH, VC and SCC were 7.85±1.52, 13.83±1.69 and 29.46±2.03, respectively, presenting significant differences. Immunostaining of type IV collagen and laminin in VH and VC displayed intact basement membrane, but presented non-continuous banding type in SCC. In light of the above results, we suggest that a combination of AgNORs and immunohistochemical staining of PCNA, type IV collagen, and laminin might be used as a method for distinguishing the differences among oral VH, VC and SCC.