Here, we evaluated the CD68+ macrophage numbers during HNSCC progression in a large clinical series composed of 10 cases of tumor-free peri-tumoral epithelia (TFE), 43 cases of low-grade dysplasia (LGD), 45 cases of high-grade dysplasia (HGD) and 110 cases of carcinoma (CA), including 74 cases of HPV-negative and 36 cases of HPV-positive HNSCCs. The gene discussed is CD68; the disease is head and neck squamous cell carcinoma.