© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. Racial disparities in cancer mortality still exist despite improvements in treatment strategies leading to improved survival for many cancer types. In this study, we described race/ethnic differences in patterns of de novo metastasis and evaluated the association between site of de novo metastasis and breast, prostate, and colorectal cancer mortality. Data were obtained from the Surveillance Epidemiology and Ends Results (SEER) database from 2010 to 2013 and included 520,147 patients ages ≥40 years with primary diagnosis of breast, colorectal, or prostate cancer. Site and frequency of de novo metastases to four sites (bone, brain, liver, and lung) were compared by race/ethnicity using descriptive statistics, and survival differences examined using extended Cox regression models in SAS 9.4. Overall, non-Hispanic (NH) Blacks (11%) were more likely to present with de novo metastasis compared with NH-Whites (9%) or Hispanics (10%). Among patients with breast cancer, NH-Blacks were more likely to have metastasis to the bone, (OR: 1.25, 95% CI: 1.15–1.37), brain (OR: 2.26, 95% CI: 1.57–3.25), or liver (OR: 1.62, 95% CI: 1.35–1.93), while Hispanics were less likely to have metastasis to the liver (OR: 0.76, 95% CI: 0.60–0.97) compared with NH-Whites. Among patients with prostate cancer, NH-Blacks (1.39, 95% CI: 1.31–1.48) and Hispanics (1.39, 95% CI: 1.29–1.49) were more likely to have metastasis to the bone. Metastasis to any of the four sites evaluated increased overall mortality by threefold (for breast cancer and metastasis to bone) to 17-fold (for prostate cancer and metastasis to liver). Racial disparities in mortality remained after adjusting for metastasis site in all cancer types evaluated. De novo metastasis is a major contributor to cancer mortality in USA with racial differences in the site, frequency, and associated survival.