Barcelona coach Tito Vilanova will have surgery on a saliva gland on Thursday followed by six weeks of chemotherapy and radiotherapy.
Vilanova had a cancerous tumour removed from the gland at the back of his throat in November 2011.
The 44-year-old is expected to be in hospital for three to four days, but going forward he "could be able to mix work with his treatment", says Barca.
Assistant coach Jordi Roura will take charge of the team in the meantime.
In a news conference on Wednesday, Barcelona president Sandro Rosell said: "We want to express our unconditional support to Tito and his family.
"Tito is strong, very strong, he's shown us that and we're convinced that he'll be back with us soon.
"We have complete confidence in the team. The club is very strong and very united, we're capable of overcoming adversity."
Real Madrid posted a message of support for Vilanova on their website, which read: "Real Madrid want to express their support and best wishes for the coach of FC Barcelona, Tito Vilanova, and wish him a very rapid recovery.
"Real Madrid offer their support to his club and to all his family."
Former Barcelona striker Gary Lineker tweeted: "Very sorry to hear Tito Vilanova, the Barca coach, is undergoing surgery after a cancer relapse. Thoughts are with him."
Manchester City striker Sergio Aguero tweeted: "We support you, #AnimoTito! We wish you the strength to overcome this moment."
Former tennis world number one Rafael Nadal tweeted: "All my strength and support for Tito Vilanova! We are all with you to overcome this next hurdle."
Vilanova's 15-year-old son Adria, a member of the club's youth team,tweeted: "Many thanks to everyone for the support. You're great, everything will be fine. Greetings."
Vilanova was Pep Guardiola's assistant at the Nou Camp before replacing the former Spain midfielder, who has taken a sabbatical from football, in June.
Since taking charge of the Catalan club, Vilanova has won 23 of his 27 matches in all competitions.
The La Liga leaders are nine points clear of second-placed Atletico Madrid after 15 victories in their 16 matches in the Spanish top flight.
They have also qualified for the knockout stages of the Champions League, despite one of their two defeats this season being inflicted by Group G rivals Celtic.