Overall survival from cancer has greatly improved, although it still remains the second leading cause of mortality in the world. This result was achieved through the use of chemotherapy and radiotherapy, which are severely toxic to normal tissues. In the long-term follow-up of cancer patients, the development of secondary malignant disease is common and it is one of the most severe side effects of cancer treatment. Physicians aim to decrease this toxicity and reduce the development of secondary cancers. In this study, the epidemiology and etiology of second malignant neoplasms are reviewed.