Fibro-osseous lesions (FOLs) are a poorly defined but pathologically diverse group of lesions
affecting the craniofacial bones and jaw. They are mostly characterized by the replacement of
bone by a benign connective tissue matrix, which may contain foci of mineralization in the form of
woven bone or cementum-like round acellular intensely basophilic structures. These lesions, although
diverse, often present similar clinico-pathological and radiographic features. This often leads
to difficulty in diagnosis and management. Definitive diagnosis is often reached only by incisional
or excisional biopsy in resource-limited settings. Epidemiologically, the incidence and prevalence of
different FOLs have been variable depending on the region. Reports from Africa indicated that
FOLs make up to 10% of all oral biopsies, while others have given lower figures. A good understanding
of the pathogenetic mechanism for FOLs is important, and state of the art molecular approaches
are bound to improve the diagnosis and delineation of various entities that fall under the
FOL category. Not least, the classification and nomenclature of these lesions by the World Health
Organization (WHO) have changed significantly over the years. Hence, we have presented in this
review a robust discussion on the pathobiology, emerging molecular markers, diagnostic challenges,
future perspectives and recent changes to the classification/nomenclature of FOLs by WHO. In addition,
we also discussed the diagnostic bottlenecks encountered during diagnosis of FOL in Africa.