Oral papillary lesions include a variety of reactive, developmental, and neoplastic conditions. Inflammatory papillary lesions almost involve the hard palate and are usually associated with the use of ill-fitting dentures and poor oral hygiene. Contrarily, perioral involvement of papillomatosis can also be found in neoplastic or syndromic conditions. This case report aimed to present a 44-year- old male patient with rarely encountered multifocal non-human papillomavirus (HPV) inflammatory papillary hyperplasia and evaluate the differential diagnosis that represents similar clinical and histopathological conditions. Multifocal papillary lesions on the lips, tongue, alveolar crest, and oral mucosa were surgically removed via scalpel and laser application. The histopathologic examination confirmed the diagnosis of non-HPV inflammatory papillary hyperplasia. Complete recovery was achieved and the patient was rehabilitated with a new removable prosthesis. Surgical removal of the papillary lesions seems to be a reliable treatment option. In addition to HPV-induced lesions and poor oral hygiene, other etiologic factors should be eliminated with clinicopathologic consultation and genetic investigations.