Abstract Introduction: Living within proximity to hazardous waste (superfund) sites can pose an increased risk of exposure to chemicals of concern, including cancerogenic substances. Per- square mile, Puerto Rico has a high density of contaminated sites, including the designation of 19 superfund sites by the Environmental Protection Agency across the archipelago. Understanding how living within proximity to superfund sites can help recognize communities that are at greater health risks, such as increased cancer risks. Objectives: Identify clusters and outliers for all types of cancer, to assess ecological risk, by the presence of superfund sites across Puerto Rico. Methods: All types of cancer were recorded and provided by the Puerto Rico Central Cancer Registry for the period of 2010-2020. This data was summarized by municipalities (n=78). Cancer cases in each county were aggregated and divided by population in 2020 to show prevalence of cases. Using geographical information systems (ArcGIS), a Local Moran’s I was run to identify potential municipalities that have clusters; location with similar high (hot spots) or low values (cold spots) and outliers; locations with dissimilar values from their surrounding neighbors. A layer representing municipalities with superfund sites was also applied to the map to see if there was a relationship between living in a superfund site and cancer risk. This study was approved by UPRCCC IRB Protocol #2023-11-124. Results: Between 2010 and 2020, a total of 114,560 diagnosis occurred for all types of cancer in PR, from which 48.06% accounted for females and 51.93% for males, with breast and prostate as the primary cancer sites, respectively. Our analyses showed one hotspot and three cold spots with statistically significant differences from their neighboring municipalities. One hotspot was in Canovanas (p=0.03) which has a superfund site related to pharmaceutical chemicals. The three coldspots were in Cataño (p=0.04), Trujillo Alto (p=0.04), and Guánica (p=0.03). Additionally, four high and low outliers were identified. Across the municipalities, in the lower outliers Vega Alta (p=0.04), Corozal (p=0.002) are the only ones with current Superfund sites. Cabo Rojo (p=0.002) and San German (p=0.006) are included in the list of higher outliers, which are places with superfund sites. However, Hormigueros (p=0.03), and Arroyo (p=0.03), are also in this category. Conclusion: The results identify the key cancer clusters and outliers across municipalities in comparison to neighboring municipalities on the island. Results show municipalities with and without Superfund sites as part of the higher outliers list, which additional research could help establish other contributing factors. Further analysis is needed to consider what factors affect the clusters such as age range, type of cancer, and presence of other environmental contaminants in the area. Acknowledgements: This research was supported by award 1R25CA240120-01 (Cancer Prevention & Control Research Training Program) from the National Cancer Institute. Citation Format: Sailing JT Tang, Nancy R. Cardona, Ana P. Ortiz. Superfund sites and cancer risk: Cluster analysis in Puerto Rican municipalities between 2010 and 2020 [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A057.