Background: Sexual hormones have an important role in many hormone-dependant tumors like breast and prostate carcinomas, and also a relationship has been found with bone metabolism and bone tumors. Some studies have demonstrated that the expression of hormonal receptors (HR) in osteosarcomas (OS) of long bones is associated with gender, histological grade, histological type, and possibly may be connection with pathogenesis and evolution. However, to our knowledge there are no studies of HR in osteosarcomas of craniofacial bones (OS-CF). Objectives: To assess the expression of hormonal receptors in OS-CF. Material and Methods: Twenty one cases of OS-CF were included in this study. Clinical outcome was obtained from clinical charts. Histological sections were reviewed, and immunohistochemistry studies for estrogen, progesterone and androgen receptors were performed. Results: A striking female predominance was found (2:1), with a median age of 35 years. The predominant type of OS was osteoblastic (52.4%), and histological grade was high in 86%. Follow-up was obtained in 13 cases and ranged from 6 to 118 months (median 29 months). There were 8 patients (61.5%) dead or alive with progressive disease in the last follow up. Negative expression of HR was found in 19/21 cases; one showed weak nuclear expression for estrogen receptor, and another for androgen receptor. Progesterone receptor was negative in all cases. Conclusions: OS-CF mostly affected females, most of them were of the osteoblastic type and of high grade. Hormonal expression was practically negative in osteosarcoma of craniofacial bones.