The history of human and animal cancers date back to antiquity. The earliest written document on cancer appeared on Egyptian papyrus. For centuries, the theory of "four humors" was the primary hypothesis that explained the cause for cancer. Finally, in the 19th century a new era began with the detection of the cellular origin of cancer; in due course, the nature of this lethal disease was better recognized and led to further achievements in cancer treatment. During the 20th century researchers investigated several risk factors for cancer such as tobacco smoking and environmental chemicals, in addition to the carcinogenic role of certain viruses, occupational association of cancer, its relationship with certain hormones and dietary habits, and the genetic basis of cancer. These investigations resulted in more efficient cancer management. After the advent of radiotherapy and chemotherapy as two complementary therapeutic modalities to surgery, the campaign against cancer has improved. However, cancer remains a major health challenge that accounts for substantial morbidity and mortality worldwide. The present paper briefly reviews the history of cancer in Iran, particularly during the last decades of the 20th century.