Introduction: The vocal fold is vulnerable to several types of lesions. Immunohistochemistry is a technique aimed to complement the routine histopathological investigation, showing the presence of different antigens in the tissue or cell by means of specific antibodies, thus allowing the assessment of the potential proliferation of neoplastic cells. Objective: Detailed review of the results of vocal fold biopsies and correlation between histopathological data and clinical course among patients. Methods: A descriptive retrospective study based on the analysis of medical records of patients undergoing laryngeal microsurgery due to benign diseases (polyps and nodules), whose biopsies required additional investigation using immunohistochemistry techniques. All biopsies were carried out by the same specialist, from January 2018 to December 2019 at the Hospital Paranaense de Otorrinolaringologia. Results: Seven out of the 29 patients included in this study (26 male and 3 female patients) claimed to be tobacco users. All the 18 patients investigated for high-risk HPV scored negative in diagnostic immunohistochemistry. Three of the 19 patients with suspected laryngeal papillomatosis resulted in squamous cell carcinoma in the anatomopathological examination. Conclusion: Due to similar histopathological aspects between the different types of vocal fold lesions, there is considerable doubt regarding the gold standard in histopathological examination. To determine the difference between benign lesions of the larynx, this paper reinforce the major role of performing immunohistochemistry examinations in the diagnosis of apparently benign lesions regarding early diagnosis and treatment.