The occurrence and frequency of neoplastic lesions in ancient populations has been a subject of debate for both paleopathologists and medical historians. The available sources of information are both direct, i.e., deriving from the study of ancient skeletal or mummified samples, and indirect, i.e., deriving from the analysis of ancient works of art, and of written records. Often, however, indirect sources do not allow a precise nosographic identification of the disease. Therefore, paleopathology is critical for the study of tumors in antiquity. The paleopathological record is itself difficult to interpret, because of the relative scarcity and poor state of preservation of the samples generally available for analysis. The study of the antiquity of tumors can be conveniently approached following a geographic criterion. Tumors are already documented in fossil specimens referred to an early ancestor of modern humans, Homo erectus. However, neoplastic lesions become relatively abundant only from the Neolithic period. Altogether, in ancient populations from Africa, Eurasia and the Americas, some benign tumors and most malignant soft tissue tumors may have had a frequency comparable to that documented for modern populations. In contrast, carcinomas and hemopoietic tumors which occur frequently in modern populations appear to have been generally rare in antiquity. To a large extent, this was probably related to the demographic structure of ancient populations. However, some malignant tumors, including nasopharyngeal carcinoma in ancient Egypt, and multiple myeloma in Africa, Eurasia, and the Americas, may have occurred more frequently in the past.