In March 2007, Wayman Tisdale underwent treatment for cancer of the knee (osteosarcoma), which was discovered after he fell down a flight of stairs in his home and broke his leg.

In May of that same year, Tisdale announced he was recovering from a procedure to remove the cyst, and expected to make a full recovery. However, after a series of chemotherapy treatments the cancer later returned.

 In August 2008, Tisdale had part of his right leg amputated because of the bone cancer.

 On his web site, Tisdale said removing a portion of the leg would be the best way to ensure that the cancer would not return. Shortly after the operation, Wayman was fitted for prosthesis. It was this experience coupled with the knowledge that the process is not always covered by health insurance that led Tisdale and his wife, Regina to begin work on the establishing the Wayman L. Tisdale Foundation.

Tisdale died on the morning of May 15, 2009 at St. John Medical Center in Tulsa, Oklahoma. The Foundation was officially established shortly after.