[4] The Roswell Park campus, spread out in 15 separate buildings of approximately two million square feet, occupies 28 acres (11 ha) on the 100-acre (40 ha) Buffalo Niagara Medical Campus (BNMC) in downtown Buffalo, and includes 1,500,000 square feet (140,000 m2) of space equally distributed between clinical programs and research/education functions.

In 1898, the program that would later become the cancer center was established by Roswell Park, who was a professor of surgery at the University of Buffalo School of Medicine.

Seeing the importance of dedicated cancer research, select Buffalo citizens donated funds to purchase land and construct a new building.

Gerty and Carl Cori jointly won the 1947 Nobel Prize in Physiology or Medicine, "for their discovery of the course of the catalytic conversion of glycogen.

"[13] Their research leading to the discovery began during their tenure at Roswell Park (then called the New York State Institute for the Study of Malignant Diseases), from 1922 to 1931.

[15] In 1975, Thomas Dougherty successfully treated preclinical models of cancer using photodynamic therapy (PDT) techniques for the first time.

Biochemist Marie Hakala, PhD[22][23] first observed that 5-fluorouracil becomes more effective in treating cancer cells when calcium leucovorin is added.

[28] Roswell Park Comprehensive Cancer Center has received numerous accolades for the quality of healthcare provided.

[47][48] Roswell Park was the first American institution to receive FDA permission to conduct clinical trials of CIMAvax, a Cuban medical therapy developed by Centro de Immunologica Molecular, La Habana, Cuba.