OBJECTIVE To describe and compare trends in leukemia mortality among children (0-14 years of age) and adolescents and young adults (AYA, 15-24 years of age) in 12 countries in Latin America during 1980-2004. METHODS Data from the World Health Organization mortality database was analyzed using a joinpoint regression model to identify significant mortality rate changes over time and to estimate annual percent change. RESULTS Leukemia is ranked first among cancer-related causes of death among children and AYA in Latin America. In children, the global percentage changes indicate increased rates for both sexes in Colombia, Ecuador, and Mexico, with substantially higher rates for Mexico. In AYA, significant increases were observed for both sexes in Mexico; Ecuador saw some increase for both sexes; and Colombia and Uruguay had increases in females only. Downward trends were observed in Argentina for both sexes, and in Costa Rica for males only. There were no major changes in the other countries analyzed. CONCLUSIONS Leukemia mortality rates among AYA are declining, but show less significant decreases than rates among children. The study results point to a global need for further advances, specifically for AYA, similar to those made by childhood leukemia therapeutic protocols. Also, specialized oncological centers exist in most countries of Latin America, but they are often inaccessible. Special attention should be given to Mexico due to the significant increase in mortality rates.