The Uganda Cancer Institute started with the initiation and development of the Lymphoma Treatment Centre (LTC) which was a result of corporation and hard work of many individuals at the Makerere University medical school, Ministry of Health (MOH) and the National cancer institute (NCI) in the USA.

The success of the Lymphoma treatment center lead to the foundation of a sister unit the Solid Tumor Centre (STC) in 1969 to enable additional investigations in adult cancers especially hepatocellular carcinoma, Kaposi's sarcoma and malignant melanoma to be carried out. Functioning jointly, the two units STC and LTC together with the associated laboratories formed the Uganda Cancer Institute (UCI).

The first report of the efficacy of chemotherapy alone in childhood Hodgkin’s disease came from the Institute, at a time when radiotherapy was the main modality in resource-rich countries for management of earlystage disease. A comprehensive description of adult and childhood endemic Kaposi’s sarcoma, response to treatment and early observation of an epidemic form of the disease in Africa came out of the Institute. The initial attempt at objective staging of hepatocellular carcinoma was the Kampala Staging Scheme, which was devised at the Institute and presented at the international symposium on liver cancer held in Kampala in 1971.

This was to be followed by the landmark report on the efficacy of adriamycin as a single agent in hepatocellular carcinoma. Given the challenge of the availability of chemotherapy in developing countries noted at the onset, the Institute proposed the concept of an essential drug list for cancer therapy which has since been accepted and adopted by the WHO as a key component of the global cancer control effort.

On 3rd October 2014, African Development Bank together with the Ugandan government sign an agreement to finance the establishment of Uganda Cancer Institute as the East African Center of excellence for oncology providing leadership in Cancer related trainings and services in the East African region.

The Fred Hutchinson Cancer Research Centre in Seattle and the USAID completes a modern outpatient, a research laboratory and training center. The UCI/HCCA is a partnership between the UCI and Fred Hutchinson Cancer Research Center (Fred Hutch) that seeks to reduce the global cancer burden through the prevention, early detection, diagnosis and treatment of cancer, infectious diseases and other related health concerns in Uganda.

A six level cancer building comprising an imaging centre, clinical laboratory, intensive care unit, chemotherapy infusion centre and three levels of ward space is completed. A community cancer clinic is developed in a rural district of Mayuge; it serves as pilot project in understanding cancer burden in a rural population.

The Uganda Cancer Institute act is passed by parliament giving it a legal basis to effectively deliver on its expanded mandate under the act of offering national leadership in cancer related activities.