The existence and the pathological character of tumours has been knows in Europe since ancient times, as the earliest references to this condition can be found in the papyri discovered by Edwin Smith and dated to late 27th century, sometimes attributed to Imhotep, designer of the Sakkara Pyramid. The document in question contains a reference to a 'bulge in a breast' that was considered immune to all known methods of treatment. It is strongly suggested that malignant tumours plagued humanity from the very beginning, as the oldest cases were found in the remains of a hominid excavated in Swartkrans Cave in South Africa that were roughly 1.7 million years old.

This said, it should be noted that most cases of cancer very rarely if ever lead to a sudden death that could have been construed as 'inexplicable'. In most cases of internal neoplasms that are not immediately visible, growing tumour usually causes pain that can range from slight to excruciating, depending on the location and size, and the advanced tumours often cause the affected organs to fail, leading to various, usually quite distinct symptoms and general, often progressing deterioration of the general state of the patient. In other words, people suffering from cancer would have been usually considered 'sick' since the times immemorial, even if the doctors of the era could not have diagnosed the condition properly.

Cancers were described in length by Hippocrates in 5th century BCE. Although their presence has been explained by Greek and Roman physicians chiefly according to the principles of the humoural theory, behavioural and medical conditions have also been taken into consideration as e.g. other illnesses, physical injuries, chronic malnutrition or poisoning were thought to have influence on the formation of tumours. Hippocrates, and later also Aristotle or Galen were not only aware of the neoplasms, but also attempted to classify them according to their physical characteristics, with three major types being karkinos, phyma and oidema. The first has been named after a crab (hence the Latin term 'cancer') due to its shape characterized by the central structure and tendrils resembling crab's appendages, what strongly suggests that these were malignant neoplasms visibly infiltrating surrounding tissues. They were largely believed to be caused by the overabundance of black bile. Phyma was a name generally associated with various localized lesions and tumours, that were generally not infiltrating, suggesting they were most likely either non-malignant neoplasms or wounds and lesions that became infected or produced non-standard scar tissues. Oidema was a term reserved for various soft and usually non-tender formations, suggesting various form of cysts or benign neoplasms. Greek and Roman sources include also other terms referring to the various forms of neoplasms.

Words such as deinos (strange, worrying) and kakoethes (bad influence) are sometimes used in the context of the tumours, suggesting that although pre-modern physicians were most likely unaware of the malignancy and did not differentiate malignant and benign tumours, they were able to notice the infiltration of the surrounding tissues and most likely considered it as a dangerous symptom. Hippocrates gives an account of what was very probably a breast cancer, describing a karkinoma inside a breast that was accompanied with the bleeding from the nipple. This case was a lethal one, as the patient eventually died. Given the importance of cancerous lesions described by the Ancient physicians, it is very probable that they were aware of a potential mortal danger posed by cancer.

Many Greek Physicians, including Hippocrates, Celsus, Archigenes or Leonides (the works of the latter two are known only through quotation made by Aetius of Amida though) were discussing surgical treatments of the neoplasms in length and were largely in favour of not treating deeply-seated and well-developed cancers as this was considered very dangerous for the patient, potentially more than the neoplasm itself. They also notice that phyma is much easier to operate on than karkinoma, as the latter usually causes much stronger haemorrhage. The surgical procedures were quite similar to modern ones and included incisions of required depth followed by quick cauterization of the surrounding tissue to minimize the bleeding and then a resection of the neoplasm, with a special care being taken to not leave any cancerous tissue behind, meaning that the idea of the cancerous growth was at least instinctively understood at the time. The first definite division between the malignant and benign tumours is largely attributed to 16th-century Italian physician Gabriele Fallopio, who determined that the lesions that are firm, irregular, adhere to neighbouring tissues and are surrounded by congested blood vessels are likely to be malignant, while soft, regular an isolated tumours tend to be benign. These observations were proven to be generally correct and are used for preliminary diagnosis even today.

In addition, all methods proposed to decrease the concentration of the black bile were considered both a curative and preventive measure against neoplasms. Galen and many later physicians commonly advocated venesection (bloodletting) as an universal methods of 'equalizing humours'. Dioscorides, who lived in 1st century AD and was known for a most comprehensive ancient herbary that was an authoritative medicinal and botanical source well into the early modern era, named peavine (Lathyrus annuus), figwort (Scrophularia auriculata), squirting cucumber (Ecballium elaterium) and bugle (Ajuga arabica) as a good medicine against various tumours, although usually those that are not malignant or in case of the latter, they were cited as an useful agents facilitating post-operational recovery. He also singled out milkweed as a medicine for breast neoplasms, possibly using the principle of sympathetic relation, as the plant producing milky latex was considered to possess an affinity to milk-producing breasts, as the plant, especially the aforementioned latex is irritating and mildly toxic to humans.

Aulus Celsus, Roman scholar living in 1st century BC, also noticed that the cancerous tumours should not be removed as they are likely to return and still kill the patient, possibly observing the metastasis of undiagnosed cancer in practice. He advised that small tumours can be removed, but any advanced cancer should not be treated by excision or cauterization, as they 'are excited immediately and start to increase until they cause a death to a patient'. It is also worth noting that many of the mentioned medical authorities generally agreed that if a tumour is inoperable, it will unlikely to be influenced by any curative or dietary solution, what suggests that they were aware of the extreme danger malignant neoplasm pose to an organism, as inoperable cancer was largely considered lethal with nothing short of miracle being able to help the patient.

Paul of Aegina, Roman physician living in 7th century, noticed that although cancerous tumours most often appear in the female breasts (possibly because these are easily palpable in comparison to e.g. tumours in body cavities and thus are easiest to report by patients themselves), they can nevertheless appear in any organ. Greaco-Roman knowledge received and elaborated on by the Arab physicians also included research concerning the neoplasms. Ibn Zuhr in his Kitab al‐taysir fi al‐mudawat wa al-tadbir (Practical manual of treatments and diets) describes cancers of stomach and esophagus. Both Graeco-Roman and Arabic medical knowledge were eventually adopted by European medieval scholars, initially from the School of Salerno and other Italian learning centres and remained the mainstay of medicine until late 16th century.

So, to sum it up, cancer was known since Antiquity and although many neoplasms were not easily observable, their influence on the organism certainly was and thus the suffering associated with the cancer was explained according to any medical theory was present in a given community. It is worth noting that this mechanism was pretty much the norm of the medicine anytime before 19th century, when the advances in biology and technology (especially microscopy) allowed to understand underlying causes of many diseases that were observed, but usually were treated in a hit-and-miss fashion. And many of these diseases were possible to be cured only after the popularization of antibiotics and introduction of antiviral agents, what happened slightly over a half of century ago.