In 1866, Herman H. Hofmann, Marcellin Coté, and John C. Burgher, started to gather donations to open a hospital specializing in homeopathic medicine in Pittsburgh.

Construction for the new hospital began in 1907, completed in January 1910, and opened its doors to patients on March 1, 1910, on a site in front of its current location.

[8] In 2020 the hospital was recognized by Human Rights Campaign Foundation as a "Top Performer" in their forward thinking LGBTQ policies and initiatives.

[14] The UPMC Hillman Cancer Center in the Shadyside neighborhood of Pittsburgh is the flagship facility for the clinical services and research activities.

It is located directly across Centre Avenue from, and connected via a pedestrian bridge to, UPMC Shadyside hospital where cancer surgery and Intensity Modulated Radiation Therapy (IMRT) are conducted.