Anemia is a sign of underlying disease that is causing blood loss, sequestration of red blood cells (RBCs), impaired RBC production, or primary marrow dysfunction. The most efficient clinical approach to a patient with anemia is to ask the following three questions: Is the anemia microcytic, macrocytic, or normocytic? Is pancytopenia present? Is the marrow response appropriate for the anemia as determined by the reticulocyte count? Answers to these questions focus laboratory evaluation on a logical progression and avoid a costly shotgun approach.