Aggressive cases of central giant cell granuloma (CGCG) have been arbitrarily treated with steroids and calcitonin. The aim of this study was to develop a practical tool, based on the relative percentage of positively stained cells for glucocorticoid and/or calcitonin receptors, for selecting the appropriate therapeutic agents to treat CGCG. Forty-one formalin-fixed, paraffin-embedded blocks of CGCG were immunohistochemically stained for glucocorticoid and calcitonin receptors. Percentage of positive lesional mononuclear and giant cells was estimated for each case. Intense staining was considered as staining 50% or more of the cells. Correlations among staining scores were analysed by Spearman's test. All cases stained for glucocorticoid receptor. Heterogeneity among cases showed as intense staining in both cell types (21 lesions), in only one cell type (13 lesions) and weakly in both cell types (7 lesions). Only 23 cases demonstrated staining for calcitonin receptor, of which 15 stained intensely in both cell types and 7 in only one cell type. Among staining scores of both receptors, no significant statistical correlation was found ( P > 0.05). It can therefore be suggested that the relative percentage of immunohistochemically stained mononuclear and giant cells for glucocorticoid and/or calcitonin receptors can serve as a reliable and practical tool for selecting the appropriate therapeutic agent to treat CGCG. The clinical application of this method should be assessed in well controlled clinical studies, especially in cases of aggressive lesions, before initiating and during therapeutic treatment.