Objective: Central giant cell lesions (CGCL) and peripheral giant cell lesions (PGCL) occur in the jaws and contain osteoclast-like giant cells and mononuclear cells positive for the macrophage marker CD68. The participation of immune-inflammatory mechanisms has been proposed in the lesions development. As IL-10 is one of the most important anti-inflammatory cytokines and it is also an inhibitory cytokine to macrophage function and bone resorption, the purpose of the present study was to investigate its expression together with its receptor (IL-10R?) in CGCL and PGCL. Study Design: Six fragments of CGCL and seven fragments of PGCL were obtained by surgical excision. Frozen specimens were cut and subjected to immunofluorescence staining using fluorescent-labeled anti-CD68, anti-IL-10, and anti-IL-10R? monoclonal antibodies. Microscopic analyses were performed and the percentage of positive mononuclear and giant cells for each parameter was obtained. Results: Our results revealed that all giant cells from CGCL and PGCL were CD68+ and IL-10R?+ and that the majority was also positive for IL-10. More than 50% of the mononuclear cells from both lesions expressed IL-10R? and the majority of these cells were CD68+ and IL-10+. Conclusion: Considering that IL-10 has inhibitory effects on the pathologic processes related to the development of the oral giant cell lesions, the high frequencies of cells producing this cytokine seems contradictory to these lesions growth. Investigation about the production of inflammatory cytokines as well as the IL-10 signaling pathways in oral giant cell lesions is required to elucidate the immunopathology of CGCL and PGCL. © Medicina Oral S. L.