Knockdown of CaMK2α by lentivirus shRNA in aggressive osteosarcoma MG-63 and 143 B cells significantly decreased proliferation, migration, and invasion in vitro and reduced tumor burden in vivo; in contrast, overexpression of CaMK2α by retrovirus in nonaggressive and nontumor forming osteosarcoma HOS cells dramatically increased cell proliferation, migration, and invasion in vitro, resulting in tumor formation in vivo. This evidence concerns the gene CAMK2A and osteosarcoma.