Marcello Crescenzi was born in Rome in 1500, the son of Mario Crescenzi and Pantasilea Capodiferro.^[1]

He became a doctor of both laws.^[1] He was a canon of Santa Maria Maggiore.^[1] In 1525, he was made an Auditor of the Roman Rota.^[1]

On 19 January 1534 he was elected Bishop of Marsi.^[1] He resigned the government of the diocese sometime before 17 May 1546.^[1]

Pope Paul III made him a cardinal priest in the consistory of 2 June 1542.^[1] He received the red hat and the titular church of San Marcello al Corso on 6 November 1542.^[1]

On 2 November 1544 the pope appointed Cardinal Crescenzi to the Council of Trent.^[1] On 5 May 1546 he became administrator of the see of Conza, holding that position until his death.^[1]

He was a cardinal elector at the papal conclave of 1549-50 that elected Pope Julius III.^[1] The new pope made Crescenzi papal legate in Bologna.^[1] He was the Camerlengo of the Sacred College of Cardinals from 19 January 1551 to 8 January 1552.^[1] The pope named him to a commission on church reform on 18 February 1551 and, on 4 March 1551, named him legate a latere to the Council of Trent.^[1]

He died in Verona as he was returning to Rome from Trent on 28 May 1552.^[1] His remains were returned to Rome and he was buried in Santa Maria Maggiore.^[1]