In 2006, he moved to La Liga club Real Madrid, where he won a league title, but was chastised for his poor behaviour, inconsistent performances, and work-rate, and returned to Italy a year later, on loan to Sampdoria.

[12] He was raised in poverty by his mother in the San Nicola district of the Bari Vecchia neighbourhood, and began playing football on the streets at an early age.

[14] During his time with Bari, he soon emerged as one of Serie A's most promising young Italian players, drawing particular attention to himself after scoring a notable, individual, match-winning goal (his first ever Serie A goal) in a 2–1 home win over Italian giants Inter Milan, on 18 December 1999, at the age of 17: in the 88th minute, after controlling a 40-yard lobbed pass on the run with his backheel, he subsequently dribbled past veteran defenders Christian Panucci and Laurent Blanc, wrong-footing goalkeeper Fabrizio Ferron with a dummy, before finishing at the near post.

[13][20] His first season produced five goals, as well as a 2001 Supercoppa Italiana victory, and he attracted media attention after openly clashing with coach Fabio Capello after he was left out of a practice match a few days after his international debut.

[21] In the 2003 Italian Cup final against Milan, Cassano was sent off after protesting an official's decision, and he flashed the sign of the horns at the referee while leaving the pitch.

[26] On 30 October, Real Madrid's official website announced that Cassano had been suspended due to his "disrespect" of Capello, who had joined the club at the beginning of 2006–07 season, following a dressing room argument arising from his omission from the team after a game against Gimnàstic de Tarragona,[27] and was subsequently benched along with David Beckham and Ronaldo.

[28] In an interview with Spanish radio in July 2007, Real Madrid president Ramón Calderón described Cassano's attitude as "unsustainable in the last couple of months" and indicated that he would be leaving the club.

[30] He made his Sampdoria début that season in the Derby della Lanterna against Genoa on 23 September, in which he was substituted by former Roma teammate Vincenzo Montella in the final minutes of the match.

Sampdoria ended the season with an UEFA Cup berth, while Cassano was acquired on a permanent basis by the club on free transfer (plus bonus) from Madrid.

[33] After the January signing of Giampaolo Pazzini from Fiorentina, Cassano managed to form a fruitful striking partnership with the former Viola forward, that was praised by both media and Sampdoria supporters, and led club chairman Riccardo Garrone to compare it with striking duo of Gianluca Vialli and Roberto Mancini that led Sampdoria to win their only Scudetto to date,[34] an opinion that was later shared also by both Vialli and Mancini.

However, a result crisis, including a 3–0 defeat in the local derby against crosstown rivals Genoa, left Sampdoria down to mid-table on January, leading head coach Luigi Delneri to put Cassano off the team for "technical and tactical reasons", casting doubts about the player's future at the club.

In the final days of the January transfer window, he was linked with a move on loan to Fiorentina, that was however denied with an official statement from the club,[39] but was described by the media as Cassano's own refusal to leave Sampdoria.

[40] This was confirmed by Cassano himself through an official statement published on Sampdoria's website, citing his relationship with club chairman Riccardo Garrone, his teammates and the team supporters as the main reason for his choice.

In October 2010, Cassano was excluded from the first team squad with immediate effect after he had a heated row with chairman Riccardo Garrone following the player's refusal to attend an award ceremony.

[44] Following such events, Sampdoria formally applied for a contract termination to a league arbitration panel, a position that was confirmed even after Cassano apologised to Garrone and the club.

[46] On 20 December 2010, it was reported that Milan, Sampdoria and the player agreed the installment plan to pay a €5 million to Real Madrid which was indicated in Cassano's buy-out clause when he left the Spanish club.

[51][52][53] He returned to the first team on 7 April 2012, after almost six months on the side-lines, featuring as a substitute in Milan's 2–1 home defeat to Fiorentina in Serie A, and received a standing ovation from the crowd as he entered the pitch for Gianluca Zambrotta in the 79th minute.

[62] On 21 August 2012, Milan and Inter reached an agreement over an exchange deal involving Giampaolo Pazzini and Cassano, with a compensatory sum of €7.5 million in favor of the Nerazzurri.

[69] Cassano's work-rate, fitness and discipline improved at Parma, as he managed to keep control of his weight through a stricter diet and training regime, losing 10 kg.

[8] In the first half of the 2014–15 season, Cassano managed 5 goals in 20 appearances as Parma were rooted to the bottom of the table and battling serious financial difficulties.

[82] He appeared in two summer friendlies for the club the next week; however, on 18 July, he was involved in a curious incident, which gained much publicity in the media: he initially communicated that he would be retiring from football, as he missed his family too much, before holding a press conference later the same day, in which he announced that he had reversed his decision, and stated that he was looking forward to "having a fun season" with Verona.

[83] However, on 24 July, he overturned his decision once again, stating that he would be leaving the club and retiring from football, commenting: "As opposed to what appeared on my wife’s official social profiles, I would like to clarify the following.

A creative forward, or fantasista, in Italian,[116][117] who usually functioned as an assist provider in his teams, due to his ability to create chances for teammates[117][118][119] (Cassano himself once stated that he preferred creating goals to scoring them),[120] Cassano was capable of playing anywhere along or behind the front-line, on either flank or through the centre of the pitch; in addition to his usual role as a second striker, he was able to act as an advanced playmaker, and was also deployed in a central role as a main striker, as a false-9, or even as a winger on occasion.

[133][134] Although he was initially regarded as one of the most promising young players of his generation,[16] even being described as Roberto Baggio's heir,[135] due to his inconsistency, difficult character, and unpredictability, many in the sport, including his former manager Fabio Capello, have argued that he did not live up to the potential he demonstrated in his youth, and that his personality affected his career.

[138] He successively joined fellow friends and former Serie A footballers Christian Vieri, Daniele Adani and Nicola Ventola in a regular Twitch show named Bobo TV, which started in 2020 during the first COVID-19 lockdown in Italy.

[139] Cassano got engaged to water polo player Carolina Marcialis in 2008, then married on 19 June 2010 at a church, Chiesa di San Martino, in Portofino.

[142] In addition to his skill, Cassano is known for his temper, poor behaviour and lack of discipline; these have led to several controversial incidents both on and off the pitch throughout his career, which have thus been dubbed Cassanate by the press and his former manager Capello.

[10][13][129] During a Euro 2012 press conference, Cassano stated his preference for there to be no gay players on the squad and used a derogatory descriptor; he was subsequently fined by UEFA for making homophobic comments.

It occurred following Friday's training session and had started off as a relatively normal discussion before the pair got into a heated slanging match, then degenerated into pushing and shoving before the other players intervened to pull them apart.

[145] Cassano was a brand ambassador for Diadora, and wore their Evoluzione K Pro GX 14 football boots in black and fluorescent yellow throughout his career.