Our progress in understanding and treating pediatric acute leukemia and lymphoma is one of the success stories of cancer biology and management. Event-free survival for children with acute leukemia or lymphoma has improved progressively during the past four decades. The advances in the cell and molecular biology of acute leukemia and lymphoma that have been made can help determine both prognosis and therapy; however, the pathologic evaluation of bone marrow and lymph node specimens must be directed appropriately to benefit from these advances. We present guidelines for the pathologic evaluation of bone marrow and lymph node specimens to maximize the chance that each patient will benefit from our increased understanding of these diseases.