Verrucous carcinoma (VC) is a rare and distinct clinicopathologic variant of well-differentiated squamous cell carcinoma (SCC). This study aims to evaluate the histomorphology, proliferative activity, level of angiogenesis, and DNA ploidy of these pathological entities. This was a retrospective-prospective study of 18 cases of verrucous hyperplasia (VH), 41 cases of VC, and 44 cases of SCC. Immunohistochemical analysis for Ki-67 (MIB-1) and CD34 were performed. The tumor proliferative index, endothelial proliferative index and microvascular density were calculated. DNA ploidy was determined using image cytometry. The age range and gender ratio were similar in all three groups. The differences in MIB-1 labeling index (p = 0.0001), microvascular density (p = 0.01), and endothelial proliferative index (p = 0.001) between VC and SCC were found to be statistically significant. A non-significant increasing trend was observed in all of these parameters between VH and VC. On ploidy analysis, 100 % of SCC cases were aneuploid, compared to 39 % of VH and 86 % of VC cases. Our study demonstrates a significant difference in tumor proliferation, microvessel density, and ploidy between VC and SCC while increasing trend between VH and VC. These parameters, along with morphological findings, may be useful in differentiating these entities in small mucosal biopsies.