Background: Acute leukemia is the most common cancer in childhood. Analyzing the spatial distribution of acute leukemia may generate the identification of risk factors. Objective: To study the incidence rate of acute leukemia, its geographic distribution, and cluster detection in the metropolitan area of Guadalajara, Mexico. Methods: We included children under 15 years of age diagnosed with acute leukemia during the period 2010-2014 in the metropolitan area of Guadalajara. Each case was geo-referenced to street level to latitude and longitude coordinates using Quantum Geographic Information System (QGIS). Spatial clusters were found in the location of the acute leukemia cases applying the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm with R statistical software. Results: A total of 269 cases of leukemia were registered, 227 (84%) were acute lymphoblastic leukemia and 42 (16%) acute myeloblastic leukemia. The mean age was 6 ± 4 years. The mean incidence of acute leukemia was 6.44 cases/100,000 inhabitants: El Salto 10.12/100,000, Guadalajara 7.55/100,000, and Tlaquepaque 6.74/100,000. The DBSCAN found three clusters, all located within the municipality of Guadalajara. Conclusions: The incidence of acute leukemia in our population is higher than that in Canada and the USA. We found three spatial clusters of childhood acute lymphoblastic leukemia in the municipality of Guadalajara, suggesting the presence of local predisposing factors. (REV INVES CLIN. 2017;69:159-65)