Vilanova led Barcelona during the 2012/13 season after taking over from Pep Guardiola, but was forced to resign last summer because of ill health.
Messages of condolence poured in from around the world for a man who also spent four years as Guardiola's assistant at Camp Nou. In their time together, Barca won three league titles, two Copa del Reys, two Champions Leagues and two FIFA Club World Cups under the duo's leadership.
Vilanova was first diagnosed with parotid gland cancer in November 2011 and the disease returned in December 2012.
He was absent from the team from December, undergoing surgery and treatment in New York as his assistant Jordi Roura took charge, but returned in late March and still won the Primera Division again - with a record points haul - before stepping down in July last year.
Messi, the fulcrum of his team, posted on his Facebook page alongside a picture of the pair: "I will never forget Tito. Forever with you. All my love to his family."
Andres Iniesta posted a picture of himself with Vilanova on Twitter, writing: "I have no words. You have been and will be an example, proud to be part of your life. I'll never forget. Much strength to your family. Rest in peace coach."
Flags at Camp Nou were flown at half mast, and a minute's silence will be held before all matches in Spain's top two divisions this and next weekend in honour of Vilanova. Josep Maria Bartomeu, the club president, said on Twitter: "Tito Vilanova was a wonderful person, and will never be forgotten at FC Barcelona. Thank you for everything you taught us."