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This study evaluates the mortality experience of 6,157 chemical laboratory workers employed at United States Department of Energy facilities.All cause, all cancer and cause-specific standardized mortality ratios were calculated. Cox regression analyses were conducted to further evaluate the relation between chemical exposure and mortality risk due to selected cancers.The mortality due to all causes combined and all cancers combined were below expectation for the cohort. There were no statistically significant elevations reported among males for any specific cancer or non-cancer outcome. There no statistically significant elevations among females for any specific non-cancer and most specific cancers; however, multiple myeloma deaths were significantly elevated (SMR = 3.56; 95% CI= 1.43–7.33; number of observed deaths, n = 7). Statistically significant elevations were seen among workers employed 20+ years for leukemia using both 2- and 5-year lag periods. Also, a statistically significant positive trend of elevated lung cancer mortality with increasing employment duration was seen using both 5- and 10-year lags. A similar trend was seen for smoking related cancers among men.While lymphatic and hematopoietic cancer mortality was below expectation, a significant elevation of multiple myeloma deaths among females and an elevation of leukemia among workers employed 20+ years (possibly due to radiation and benzene exposure) were observed. A NIOSH case—control study is underway to examine more closely the relation between multiple myeloma and a variety of chemical exposures among workers employed at the Oak Ridge K-25 facility.