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Background: The osteolytic activity of odontogenic cysts and tumors is directly associated with their growth and aggressiveness. Proteins expressed by epithelial and mesenchymal cells can influence this biological event differently in indolent cystic lesions, aggressive cystic lesions, and odontogenic tumors.Methods: The objective of this study was to compare the immunohistochemical expression of factors that stimulate RANKL (Receptor activator of nuclear factor kappa-Β ligand), CatK (cathepsin K) and MMP8 (Matrix Metallopeptidase 8) and inhibit OPG (osteoprotegerin) osteoclastogenesis between dentigerous cyst (DC), glandular odontogenic cyst (GOC), odontogenic keratocyst (OKC), and ameloblastoma (AB). Paraffin-embedded sections of 9 DCs, 9 GOCs, 20 OKCs, 21 ABs, and 4 dental follicles (DFs) were submitted to immunohistochemistry. The immunoreactivity in epithelium and connective tissue was analyzed semi-quantitatively and quantitatively, respectively. Immunoexpression of the proteins was observed in epithelial and mesenchymal cells of all lesions studied.Results: The expression of RANKL and CatK was higher in OKC, AB, and GOC (p<0.005). Higher expression of OPG was found in DF and DC compared to the other markers (p<0.005). MMP8 expression was high in GOC e OKC.Conclusions: This study demonstrated the differential expression of factors that inhibit and stimulate bone resorption during the development of DC, GOC, OKC and AB. Higher expression of RANKL and CatK was observed in more aggressive lesions. OPG appears to be one of the molecules responsible for the slower growth of DC.