Background <p>Perineural invasion (PNI) is a significant prognostic factor in head and neck malignancies, influencing treatment decisions and survival outcomes. This study aims to evaluate the prevalence of PNI across different subsites and its correlation with clinical, radiological, and pathological indicators.</p> Methods <p>A retrospective analysis was conducted on 216 patients who underwent surgical management with or without adjuvant therapy between 2016 and 2019. The prevalence of PNI was assessed across different anatomical subsites, and the correlation between radiological and pathological indicators was statistically analyzed using the chi-square test.</p> Results <p>Oral cavity squamous cell carcinoma was the most common malignancy (61%), followed by tumors of the larynx, hypopharynx, maxilla, salivary glands, and skin. Radiological indicators of PNI were detected in 17.2% of oral cavity tumors, 11.1% of laryngeal and hypopharyngeal tumors, 71.1% of maxillary tumors, and 80% of salivary gland malignancies. Pathological confirmation of PNI was noted in 20.3% of oral cavity tumors, 28.9% of laryngeal and hypopharyngeal tumors, 57.1% of maxillary tumors, and 80% of salivary gland malignancies. A significant association was observed between tumor subsite and PNI detection (<i>p</i>&lt;0.001), highlighting variability in diagnostic accuracy.</p> Conclusion <p>PNI is a critical factor across multiple head and neck subsites, with maxillary and salivary gland malignancies exhibiting the highest prevalence. The discrepancy between radiological and pathological detection underscores the need for improved imaging protocols and molecular characterization of PNI. Further research is warranted to explore the biological mechanisms underlying PNI and its potential role as a therapeutic target</p>