Background: Tumor-associated macrophages (TAMs) are a crucial cellular component of human tumors, but their exact roles in tumor growth and angiogenesis during cancer progression are still subject to debate. The present study aimed to explore the impact of TAMs on tumor progression and angiogenesis in oral squamous cell carcinoma (OSCC) and oral verrucous carcinoma (OVC). Materials and Methods: For this cross-sectional study, 60 samples consisting of 40 OSCC and 20 OVC samples were chosen. Immunohistochemical staining was performed on the samples using anti-CD68 and anti-CD31 monoclonal antibodies to evaluate the frequency of TAMs and Micro-vessel density (MVD), respectively. The data were analyzed using statistical software SPSS (v. 23) and through the independent samples Student t-test, one-way analysis of variance, and Pearson’s correlation coefficient. Results: The results of our study revealed that the mean number of TAMs and MVD were significantly greater in OSCC samples compared to OVC samples (P = 0. 001) (P = 0. 004). Also, the average number of TAMs and MVD increased in the high grade of OSCC,however, the correlation between both parameters and histopathological grades of OSCC was significant only for MVD. Our study found no significant correlation between TAMs and MVD (P = 0. 005). Conclusion: Based on the results of our study, both TAMs and MVD were found to be significantly higher in OSCC samples compared to OVC samples. These findings suggest that the progression of oral cancer is associated with an increase in TAMs and vascular density. Additionally, the use of CD68 and CD31 markers may help in differentiating between these two types of tumors.