Since the implementation of the 10th International Classification of Disease in 1999, the trend in Alzheimer's disease mortality rate has not been reported. Here, the age-adjusted Alzheimer's disease mortality rate in Puerto Rico and United States from 1999 to 2004 was analyzed. The results showed an increasing trend in Alzheimer's disease mortality rate in both the United States and Puerto Rico. However in Puerto Rico, the Alzheimer's disease mortality rate (32.4/100,000) was higher than that observed in United States (20.9/100,000). Interestingly, the Alzheimer's disease mortality rate of Puerto Ricans living in Puerto Rico is much higher than Puerto Ricans living in the United States. The higher occurrence of Alzheimer's disease mortality in Puerto Rico versus the United States could be explained by factors such as coding practices, genetics, socioeconomics, and health care. These results highlight the need for comprehensive studies on factors that may influence diagnosis, death certificate coding practices, and development of Alzheimer's disease pathology in different geographical regions.