In the current study, total tumoral EGFR expression correlated with intratumoral antibody concentration, fluorescence, and tumor contrast, except for HGG, which had the highest total EGFR expression (89%, followed by HNSCC at 62% and LAC at 41%) yet received less than half the panitumumab-IRDye800 delivery observed in HNSCC (3.9 vs. 8.1 ng/mg), suggesting a delivery barrier, which was confirmed by immunohistochemical staining of tight junction protein. Here, EGFR is linked to head and neck squamous cell carcinoma.