The Coombs test, established as a clinical tool in 1945 by R.R. Coombs, usually is ordered when hemolytic anemia is suspected or if a transfusion reaction has occurred. An overview of the etiologies of these two conditions will increase oncology nurses' understanding of what is measured with a Coombs test and increase the understandings of why a Coombs test is ordered, what diagnosis is suspected, and what patient populations are at highest risk for transfusion reactions.