In 1999, the Eppley Cancer Center became a National Cancer Institute (NCI) designated cancer center.  NCI grant funding that accompanies the designation supports shared resources for research, provides developmental funds to advance scientific goals, and fosters cancer programs that draw investigators from different disciplines together.

Eugene C. Eppley was a pioneer in the hotel industry developing one of the largest privately owned hotel chains in the United States. Eppley sold the company to Sheraton Hotels for $30 million in 1956.  Eppley was a well know philanthropist and supporter of educational and medical research.  He acquired the Hotel Fontenelle in downtown Omaha in 1920, where he lived until his death in 1958.

The Eppley Center, now The Buffett Cancer Center, opened in 2017 and consists of a 10-story cancer research tower and 8-story inpatient hospital and outpatient center that includes medical, surgical and radiation oncology clinics, a 24/7 infusion center, radiology, lab services, radiation therapy and surgical services.