Pisacane started his career at Genoa, where he was initially a member of the team's youth system. At the age of 14, however, he was diagnosed with Guillain-Barré syndrome, which seriously threatened his career, as it caused him to experience temporary paralysis in his limbs. After recovering, he was promoted to the reserve side, where he remained from 2003 to 2005. He made his professional debut during the 2005–06 season, while on loan with Ravenna. After several seasons in Serie C, he was signed by Chievo on a free transfer in 2008, but joined Lumezzane in a co-ownership deal, along with his Chievo teammates Tommaso Chiecchi and Amedeo Calliari. During the 2009–10 season, he left for Serie B side Ancona. During the 2010–11 season, he remained at Lumezzane along with Francesco Checcucci. In June 2011, Lumezzane purchased the remaining 50% registration rights for Pisacane from Chievo, while Chievo bought back Checcucci. In his sole season with Lumezzane, he refused €50,000 to defeat his own team against Ravenna, becoming a hero, along with Simone Farina, of the illegal betting war; the two players were later rewarded by being named FIFA ambassadors in 2012, while Pisacane was even invited by manager Cesare Prandelli to train with the Italy national football team later that year. In August 2011, he terminated his contract with Lumezzane. The next day, he was signed by Ternana on a one-year contract, rejoining former teammate Davide Carcuro. He won Lega Pro Prima Divisione and was the losing side of Supercoppa di Lega di Prima Divisione. On 14 June 2012, he extended his contract. On 11 July 2013, he was signed by Avellino, where he remained for two seasons. On 14 July 2015, he was signed by Cagliari. He helped the club obtain promotion to Serie A during his first season with the side, and subsequently made his Serie A debut in a 3–0 win over Atalanta, on 18 September 2016 the following season, at the age of 30; having finally achieved his childhood dream of playing in the top Italian division, he was moved to tears during the post-match interview. In 2016, Pisacane was named the inaugural winner of The Guardian's Footballer of the Year award, which is given to "a player who has done something truly remarkable, whether by overcoming adversity, helping others or setting a sporting example by acting with exceptional honesty".
