Abstract Individuals with familial cancers are at increased risk of second primary cancers, and there are clear clinical guidelines for treatment and follow-up. However, the literature on the patterns of cancer family history (FH) in African Americans (AAs) is sparse. Detroit Research on Cancer Survivors (ROCS) is a population-based cohort study of AAs residing in metropolitan Detroit diagnosed with a primary invasive cancer of the breast, colon/rectum, lung or prostate after January 1, 2013. ROCS participants complete baseline and yearly follow-up questionnaires that include assessment of participants’ family history of cancer. We examined the distribution of breast, prostate, colorectal, lung, kidney, liver, ovarian, pancreatic cancers among first degree relatives and grandparents of Detroit ROCS participants (i.e, probands). We also estimated the distribution of cancers involved in known hereditary cancer syndromes (hereditary breast and ovarian cancer (HBOC), Lynch, Peutz-Jeghers, Cowden, Li-Fraumeni) within these families. Associations between probands’ age of onset and cancer family history were evaluated using logistic regression. Among the first 1,500 ROCS participants recruited into the cohort (674 breast, 138 colorectal, 174 lung, 514 prostate), 71% reported at least one relative with a cancer of any type, which did not vary substantially by proband cancer site. FH of breast (p<0.001), colorectal (p=0.010), lung (p=0.022), prostate (p<0.001), and ovarian (p=0.044) cancers significantly varied by proband cancer site, where probands were most likely to report a FH of their index cancer site (breast: 30%, colorectal: 17%, lung: 25%, prostate: 28%). When restricted to older family members (parents + grandparents), a FH of cancer matching the probands’ cancer site increased the odds of being diagnosed under the age of 50 (Breast: Odds ratio (OR)=1.73, 95% confidence interval (CI) 1.01-2.96; colorectal: OR=3.71, 95% CI 0.71-19.41; prostate: OR=1.86, 95% CI 0.91-3.79). FH of HBOC cancers was most common among probands with breast (47%) and prostate (43%) cancer compared to other sites (28-34%, p<0.001), while FH of Li-Fraumeni cancers was most common among probands with breast cancers (31% vs. 17-22%, p<0.001). Probands with breast and colorectal cancers were more likely to report FH of Cowden cancers (36-38% vs. 24-25%, p<0.001). FH of Lynch and Peutz-Jeghers cancers were less commonly reported among probands with lung (23% vs. 32-38%, p=0.004) and prostate (39% vs. 48-53%, p<0.001) cancers, respectively. AAs with breast, prostate, lung, and colorectal cancers frequently report FH of cancer, and patterns of FH differ by index cancer site. A better understanding of cancer family history among AAs could provide insights into cancer etiology in this population. Citation Format: Kristen S Purrington, Julie J Ruterbusch, Mark Manning, Michael S Simon, Jennifer Beebe-Dimmer, Ann G Schwartz. Family history of cancer among African Americans with breast, prostate, lung, and colorectal cancers in the Detroit Research on Cancer Survivors cohort [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C042.