The 28-year-old discovered that he had a form of neck cancer in October 2013 but resumed his playing career the following season after a successful bout of chemotherapy.
In a statement issued through his club, Thompson confirmed that the disease has now returned but vowed to "get the most important win of all time".
"It is with regret that I have to inform you that my cancer has returned," he said. "That given I will fight this life hurdle with the same belief, courage and desire as my previous battle. The support shown to me since I discovered my illness has returned has been immense.
"I would like to thank my wife, Chantelle, who was my rock in my first encounter and will once again be by my side with the same encouragement, discipline and strength. Not to mention the love shown to me by both my wife and beautiful daughter Thailula-Lily who are both my motivations daily.
"I would also like to thank the manager and his staff, there are no words to describe this group of people. They gave me an opportunity at the beginning of the season and I hope I have repaid their faith in me with what some say is the best form of my career. Also, to my teammates, this unique group of players who all believe in each other and keep on over-achieving.
"I came back from a goal down before, not only to equalise, but to take the lead. This illness may have found an equaliser but the quest for me to get the winner starts today and I can assure you I will get the most important win of all time."
Rochdale chairman Chris Dunphy said: "Everyone at Rochdale Football Club is greatly saddened by this devastating news. Joe is part of Team Rochdale and friend to all of us, and our thoughts are with him and his family.
"We will support Joe through this difficult time and will be with him every step of the way. He has the full support of everyone at the club and we will do everything we can to help him beat this horrible disease for a second time.
"We know he's a fighter and I've no doubt he'll fight this with the same bravery and courage as he did the last time.We wish him a full and speedy recovery."
Thompson has made more than 180 league appearances for Rochdale.