On the March 6, 2003, episode of "SmackDown!", Mysterio defeated Tajiri and Jamie Noble in a Triple Threat match to earn a shot at the WWE Cruiserweight Championship. At WrestleMania XIX, he challenged the champion Matt Hardy for the title, but lost after Shannon Moore interfered. On the May 22 episode of "SmackDown!", Mysterio defeated Shannon Moore and Crash Holly in a handicap elimination match to regain the number one contendership for the Cruiserweight title, and he defeated Hardy to win his first Cruiserweight Championship (his first reign in WWE and his first singles championship in the WWE) on the June 5 episode of "SmackDown!". Mysterio's reign ended when he lost the title to Tajiri on the September 25 episode of "SmackDown!". Three months later, on the January 1, 2004, episode of "SmackDown!", Mysterio defeated Tajiri to win his second Cruiserweight Championship. After a successful title defense against Jamie Noble at the Royal Rumble, Mysterio lost the title to Chavo Guerrero at No Way Out in February. At WrestleMania XX, Mysterio took part in a Cruiserweight Open for the title, but Guerrero retained the title. On the June 17 episode of "SmackDown!", he defeated Chavo Classic for a record-setting third Cruiserweight Championship reign. He successfully defended the title against Classic's son Chavo Guerrero at The Great American Bash. While Mysterio was Cruiserweight Champion, Spike Dudley turned heel after plowing Mysterio through a table and joined the other Dudleys before winning the Cruiserweight Title from Mysterio on the July 29 episode of "SmackDown!". At Survivor Series, he participated in a fatal four-way match for the Cruiserweight Title involving the champion Dudley, Chavo Guerrero, and Billy Kidman. Mysterio lost when Dudley pinned Guerrero to retain.