A 77-year-old woman presented with an insidious onset of fatigue and a burning sensation of the tongue on swallowing food. Six years earlier, she had undergone a total gastrectomy for early gastric cancer, which was curative. On physical examination, she was pale and had a depapillated, smooth, shiny red tongue with some central fissuring, findings that were consistent with a beefy red tongue (Panel A). Laboratory testing revealed cytopenia (white-cell count, 3400 per cubic millimeter; hemoglobin level, 6.4 g per deciliter; and platelet count, 154,000 per cubic millimeter) with macrocytosis (mean corpuscular volume, 132 fl [normal range, 80 to 100]; red-cell distribution width, 18.6%; and reticulocyte count, 2.8%) and hypersegmented neutrophils (Panel B, Wright's stain). The serum vitamin B12 level was 75 pmol per liter (55 pg per milliliter) (normal range, 160 to 970 [118 to 716]), and the serum folate level was normal. The patient received a diagnosis of megaloblastic anemia due to vitamin B12 deficiency. She was treated with intramuscular vitamin B12 and had a complete recovery after approximately 5 months. A smooth, thickened, depapillated tongue may be associated with a variety of systemic disorders, including nutritional deficiency.