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Purpose: While cancer mortality has declined by 27% between 1991 and 2016 in the United States, there are large disparities in cancer mortality by racial/ethnic groups, socioeconomic status and access to care. The purpose of this analysis is to compare trends in cancer mortality among regions (Service Planning Areas, SPAs) in Los Angeles (LA) County that vary with respect to racial/ethnic distribution and social determinants of health, including poverty, education and access to care., Methods: We estimated age- and race/ethnicity-standardized mortality for lung, colorectal (CRC) and breast cancer for eight SPAs from 1999 to 2013. We calculated three recommended measures of disparities that reflect absolute, relative and between-group disparities., Results: In all of LA County, statistically significant declines in age- and race/ethnicity-standardized mortality ranged from 30% for lung cancer to 20% for CRC to 15% for breast cancer. Despite some of the largest declines in the most under-resourced SPAs (South LA, East LA, South Bay), disparities between the lowest and highest mortality by SPA did not significantly change from 1999 to 2013., Conclusions: Despite significant declines in cancer mortality in LA County from 1999 to 2013, and in racial/ethnic groups, there was little progress toward reducing disparities among SPAs. Highest mortalities for the three cancers were observed in Antelope Valley, San Fernando Valley, San Gabriel Valley, South LA and East LA. Findings demonstrate the importance of examining regional differences in cancer mortality to identify areas with highest needs for interventions and policies to reduce cancer disparities.