In his next bout, Cazares lost the WBO junior flyweight title by split decision to Iván Calderón in Calderon's home territory of Puerto Rico.
The two faced off in a rematch, this time Cazares defeated Nashiro by unanimous decision as he captured the WBA Super Flyweight title.
Cázares successfully defended his title three times in 2010 with victories over Everardo Morales, Alberto Rossel, and Hiroyuki Hisataka.
After Hugo's defeat to Tomonobu Shimizu, he won five fights in a row over Adnan Garcia, Daniel Diaz, Rey Perez, Gabriel Altarejos and Julio César Miranda.
On 4 April 2014, Cazares came to undefeated Carl Frampton's home city of Belfast in Northern Ireland and faced him in a final eliminator for Leo Santa Cruz's WBC Super-Bantamweight World title, in the Odyssey Arena in front of an estimated crowd of 9,000 fans.