The Primera Division club's medical department revealed in a statement this evening that the 44-year-old would have surgery on his parotid gland tomorrow, before undergoing approximately six weeks of chemotherapy.
The news comes just over a year after Vilanova first had a tumour removed from his throat.
Club president Sandro Rosell expressed his "unconditional support" for Vilanova at a specifically-convened press conference this evening, in which he was flanked by on-field leaders Carles Puyol, Xavi, Andres Iniesta and Victor Valdes.
Rosell revealed assistant coach Jordi Roura would take charge of the first team while Vilanova, who took over from Pep Guardiola at the Nou Camp this summer, underwent his treatment.
The club has, however, left the door open for Vilanova to return to the touchline during his recovery, saying in tonight's statement that his "treatment may be compatible with his work life".
That decision is set to be made after tomorrow's surgery but for now Rosell offered the club's full support for Vilanova and his young family.
"Tito is strong, very strong. He's shown us that and we're convinced he'll back with us very soon," he told a press conference.
"We want to express our unconditional support to Tito and his family.
"We thank everyone for their support. We have complete confidence in the team. The club is very strong and united, we're capable of overcoming adversity."
The recurrence of Vilanova's illness was first reported this morning after Barcelona cancelled their scheduled media activities for the day.
Rossell admitted Vilanova had told him of the news yesterday, but tonight's confirmation was delayed until after a meeting with the players.
"We learned the news yesterday but Tito wanted to wait until we told the players," Rossell said. "We respected his will."
The La Liga leaders, who have enjoyed their best ever start under Vilanova this season, confirmed the speculation after the players arrived for training.
"In monitoring the process of his parotid gland, an extension of the pathology was detected, requiring surgical treatment on Thursday," a statement on the club's official website read.
"He is expected to remain in hospital for three to four days.
"After the surgery, Francesc 'Tito' Vilanova will undergo chemotherapy and radiation treatment for approximately six weeks. During this time, and depending on how well he recovers, Vilanova's treatment may be compatible with his work life.
"Keeping in line with the patient's wishes, we urge respect and privacy during this process."
Speculation in the Spanish press has already linked Guardiola, who left the club to take a year-long sabbatical in the summer, with a return, but sporting director Andoni Zubizarreta denied any contact had been made.
Barca travel to Real Valladolid on Saturday before the winter break and Zubizarreta emphasised Vilanova remained in charge.
"Tito is our coach and will continue to be our coach," he said. "Jordi (Roura) will be on the sidelines for Valladolid, but all the rest is pure speculation."
Zubizarreta also expressed his shock at the news, saying: "It was difficult news to hear this morning.
"Tito's only concern has centred on his children and his family. The only person he has not spoken of is himself."
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