Barcelona revealed last night the 44-year-old would undergo an operation on his parotid gland after a return of his illness was diagnosed.
Vilanova first had a tumour removed from his throat just over a year ago.
The Barcelona boss, who took over from Pep Guardiola in the summer, was expected to remain in hospital for three to four days before undergoing six weeks of chemotherapy.
The Primera Division leaders, who have enjoyed their best ever start to a season, said assistant coach Jordi Roura would take interim charge while Vilanova undergoes treatment.
Barcelona president Sandro Rosell offered Vilanova and his family the club's "unconditional support" at a specifically-convened press conference last night.
Rosell, who was flanked by on-field leaders Carles Puyol, Xavi, Andres Iniesta and Victor Valdes, said he expected Vilanova would quickly return to the touchline.
"Tito is strong, very strong. He's shown us that and we're convinced he'll back with us very soon," Rosell said. 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, announced as defender Eric Abidal returned to training after his liver transplant, was first reported after Barcelona cancelled their scheduled media activities yesterday.
The club eventually confirmed the speculation after players had been informed of Vilanova's condition at an afternoon training session.
"In monitoring the process of his parotid gland, an extension of the pathology was detected, requiring surgical treatment on Thursday," a statement said.
"He is expected to remain in hospital for three to four days."