We report on two patients in whom osteosarcoma occurred as second malignancy of childhood cancer. One patient had a malignant teratoma and the other adrenocortical carcinoma as the primary cancer. The emergence of cancer in cured cases and long-term survival cases of childhood cancer may result in an increase in the number of osteosarcomas seen in adolescence occurring as second malignancy. Anti-cancer drugs in large does were used for the treatment of a malignant teratoma in the former. These anti-cancer drugs may be involved in the occurrence of the second malignancy. In the latter, the patient has the germ-line mutation of p53 tumor suppressor gene, so genetic factors are presumably related to the occurrence of the second malignancy.