One of the most fundamental tenets of medical diagnosis is that when presented with a complex problem, the clinician attempts to make a single, unifying diagnosis. In approaching the problem of hemolytic anemia in the patient with cancer, it is often difficult to adhere to this tenet. The underlying diagnosis is cancer, which frequently causes hypoproductive anemias through chronic inflammation or infiltration of the bone marrow. Cancers can also cause hyperproductive anemias from blood loss and hemolytic anemias. The problem for the clinician then, is to examine the anemia in the cancer patient with the starting premise that the patient may have one, two or even three causes of anemia. Against this background, the problem of hemolytic anemia in the patient with cancer is reviewed. The causes of hemolytic anemia are divided into microangiopathic hemolytic anemia, enzymopathies, hemoglobinopathies, hemophagocytic syndrome, immune, chemotherapy-induced and hypersplenism. Each of these major mechanisms is defined and discussed in terms of pathophysiology, clinical factors and therapy.