Multifocal epithelial hyperplasia (MEH), also known as Heck’s disease, is a rare and benign condition of the oral mucosa that is strongly associated with low-risk human papillomavirus (HPV) genotypes 13 and 32. This narrative review synthesizes recent findings regarding the epidemiology, viral mechanisms, clinical and histopathological features, diagnostic strategies-including molecular and immunohistochemical methods-and therapeutic approaches to MEH. This disease predominantly affects children and adolescents from Indigenous American countries, although cases have been increasingly reported in nonendemic regions. MEH manifests clinically as multiple, asymptomatic papules or nodules, typically exhibiting a characteristic cobblestone-like appearance. Histologically, it presents with epithelial hyperplasia, koilocytosis, and altered cytokeratin expression. Molecular techniques such as polymerase chain reaction and in situ hybridization are pivotal for accurate viral genotyping, while immunohistochemical markers such as CK4/13, Ki-67, and the absence of p16 can be useful adjuncts in differential diagnosis. Despite its self-limiting nature in most cases, treatment may be warranted in symptomatic or immunocompromised patients. This review highlights the need to improve diagnostic access, develop targeted vaccines, and implement public health strategies in vulnerable communities. It also highlights existing gaps in knowledge, particularly regarding host-virus interactions and the absence of standardized treatment protocols.