The relationship between histone methylation and apoptosis, programmed cell death, is beginning to be explored. The objective of this study was to investigate the effects of staurosporine, a PKC inhibitor on the methylation of histone H3 in osteosarcoma cells. Following stimulation by staurosporine in vitro of G292 cells, a human osteosarcoma cell line with fibroblast-like phenotype, methylation of histone H3 was evaluated by western blotting and immunocytochemistry. G292 cells revealed the expression of cleaved PARP after incubation with staurosporine for 3 hours. Monomethyl lysine (K) 27 was induced by staurosporine at a concentration of 1, but no monomethyl K4 or K9 in histone H3 was seen. Dimethyl and trimethyl histone H3 K27 were also identified. There was no expression of dimethyl or trimethyl histone H3 K4 and K9. Expression of monomethyl histone H3 K27 was dose-dependent. The morphologic changes of apoptosis induced by staurosporine were observed under microscopy. Immunocytochemistry of monomethyl histone H3 K27 showed a weak signal in controls, a strong signal in staurosporine-treated tumor cells and a denser signal in the apoptotic cells. Our studies demonstrated that monomethyl histone H3 lysine 27 is expressed in staurosporine-induced apoptotic osteosarcoma cells. The findings may provide novel bridge information between the epigenetic episodes and apoptotic process