Outstanding Irish chaser Florida Pearl died on Saturday evening, aged 20, the Irish National Stud said in a statement on Sunday.
Formerly trained by Willie Mullins, the Violet O'Leary-owned gelding won the 2001 King George VI Chase at Kempton and a record-breaking four Irish Hennessy Gold Cups.
Florida Pearl had spent the last five years at the Co Kildare-based Irish National Stud, who said he had to be put down due to a rare condition linked to a malignant cancer.
A statement read: "We are saddened to inform you that on the evening of May 5, 2012, a decision was made on veterinary advice to euthanise Florida Pearl.
"The 20-year-old gelding, in residence at the Irish National Stud for five years, was diagnosed with a condition known as haemangisarcoma, a word deriving from 'malignant cancer of the blood vessels'.
"It is a rare condition which swiftly affects many organs once it spreads from its primary focus - in this case it originated in the spleen.
"Florida Pearl was a firm favourite among visitors to the INS and earned his retirement after a career which contained Grade One wins in seven seasons.
"One of the greatest steeplechasers we have seen, his speed was also obvious in his Cheltenham Championship Bumper success.
"Our thanks and sympathies go to the O'Leary family and the Mullins family, who have many memories to treasure."
Florida Pearl won 16 races, nine of which were in Grade One company, from 33 starts.
Other significant victories included the Royal & SunAlliance Chase at the Cheltenham Festival, the Martell Cup at Aintree and the Punchestown Gold Cup.
He retired from racing in February 2004 after winning his fourth Irish Hennessy at Leopardstown.Mullins said: "He was the best chaser we've ever had. "He was a huge horse in my career and he gave myself and the O'Learys some fantastic days.
"In winning a King George and four Irish Hennessys, as well as two wins at the Cheltenham Festival, his record speaks for itself.
"He enjoyed a fabulous retirement at the Irish National Stud and I'd like to thank them for the way they looked after him."
Former jockey Adrian Maguire was aboard Florida Pearl when he defeated the great Best Mate by three-quarters of a length in the King George.
He said: "He hasn't been well for a while, but it's still sad news.
"He had it all - he had size, he stayed well, he jumped brilliantly, and he also had speed.
"He was my last big-race winner in the same year I broke my neck, and as you get older you appreciate those great days even more.
"It was certainly one of my greatest days in the saddle - he was just a fantastic racehorse.
"He was also great for Ireland. He had such a great following and generated amazing interest whenever he ran.
"He'll be badly missed."
(reopens) Barry Geraghty, who won the 2002 Punchestown Gold Cup and the Martell Cup of the same year aboard Florida Pearl, tweeted: "Sad to hear of Florida Pearl's passing.
"He was a real class act and it was a pleasure to have won a few on him."