Evaluating smudge cells on the peripheral blood smear

Smudge cells are mature-appearing small lymphocytes that appear flattened or smudged on the slide; the mechanism involves vulnerability to distortion during smear preparation. Normally these cells represent <2% of nucleated cells in a blood smear; this percentage can be increased if the smear has been prepared from blood that has been sitting for ≥12 hours, in which case a repeat smear from a fresh sample can be used. The main likely causes of smudge cells are CLL in an older individual or infectious mononucleosis in a younger individual. The age cutoffs used above are approximate; clinical judgment is required.