Objectives: the expression of the osteoclastogenic cytokines TNF-?, IL-6 and IL-1? were immunohistochemically evaluated in peripheral (PGCG) and central (CGCG) giant cell granulomas of the jaws in order to determine differences between these two lesions and between the two distinct tumor cell populations (multinucleated, giant cells, MGCs and stromal spindle-shaped cells). Study Design: Paraffin-embedded tissue sections from 40 PGCG and 40 CGCG were immunohistochemically stained using antibodies against TNF-?, IL-6 and IL-l?. The percentage of positively stained cells and the staining intensity were assessed to provide a combined immunoreactivity score value. Results: TNF-?, IL-6 and IL-l? were expressed in all lesions. The CGCG compared to the PGCG showed significantly increased expression of TNF-? and IL-6 and decreased expression of IL-l? by the spindle-shaped cells and increased expression of IL-l? by the MGCs. The MGCs demonstrated in comparison to the stromal spindle- shaped cells significantly increased expression of all three cytokines in both PGCG and CGCG. Conclusions: The proinflammatory cytokines TNF-?, IL-6 and IL-l? seem to be involved in the growth process of PGCG- and CG CG of the jaws. A possible alteration in the synthesis or/and activity of these cytokines by the stromal spindle cells m the CGCGs may enhance osteolysis through the stimulation of osteoclast progenitor cells, given the fact that the intraosseous lesions cause bone resorption. © Medicina Oral S. L.