Human papillomavirus (HPV) family comprises approximately 150 known subtypes of viruses that can infect humans and other animals. Among these, HPV-16 has been shown to be associated with oral squamous cell carcinoma, particularly within the oropharynx. Here we describe the case of a patient with recurrent p-16 positive papillomatous lesions, which were successfully treated via a diode laser (445 nm) surgery. Radical treatment of HPV-related lesions can be difficult to achieve. Notably, some viruses may infect multiple oral sites and spread throughout the whole mucosa. Even after the supposed radical intervention, HPV particle remnants may lead to recurrences and new lesions. A new laser approach allows radical surgery to be performed, providing an effective method for the treatment of widespread lesions, similar to those reported here. Objective: To report a recurrent p-16 positive oral papillomatous lesion treated with a diode laser. Case report: A 26-year-old man with multiple p-16 positive oral papillomatous lesions was referred for recurrences after treatment with conventional surgery (cold knife). The lesions were successfully treated via diode laser (445 nm) surgery with no recurrence observed during the 6-month follow up. Histological examination showed immunohistochemical positivity for p16.Conclusions: Radical surgical treatment of HPV-related lesions is important to prevent recurrence and malignant transformation. Laser surgery represents an innovative treatment option.