Kelly had an initial surgery Wednesday to relieve pain on the left side of his face and jaw area. He will have another surgery a week from Tuesday and then is expected to undergo five to six weeks of radiation and chemotherapy.
"I need lots of prayers," Kelly said.
Erie County Medical Center, the Buffalo, N.Y., hospital treating Kelly, released a statement saying, "Jim Kelly came to ECMC this week for continued testing related to his oral surgery. Unfortunately, it has been determined that his cancer has returned. Our team of head and neck cancer specialists is determining a course of treatment that will allow Mr. Kelly to battle this cancer successfully. Mr. Kelly has asked that you keep him and his family in your thoughts and prayers."
Kelly underwent surgery last June to remove cancerous cells in his jaw. At the time, chemotherapy and radiation treatment were not necessary.
Kelly, who played for the Bills from 1986 to 1996, was inducted into the Pro Football Hall of Fame in 2002. He holds nearly all of the franchise's passing records.
His son, Hunter, was born with Krabbe disease, an inherited nervous system disorder. Given little more than three years to live, Hunter died at the age of 8 in 2005.
The Associated Press contributed to this report.