In most cases, the diagnostic evaluation of angioedema is challenging, as there are many possible etiologies. We report a case of an infiltrating lipoma of the tongue that masqueraded as angioedema. The patient, a 68-year-old man, presented with tongue swelling that had followed a waxing and waning course over a 6-month period. Physical examination showed a diffusely enlarged tongue with no discrete mass. A laboratory evaluation for angioedema was unremarkable. After the patient's condition did not respond to treatment with antihistamines and oral prednisone, a further workup was initiated. Magnetic resonance imaging of the neck and computed tomography of the oral cavity revealed only diffuse enlargement of the tongue. The patient underwent a tongue biopsy, which identified the cause of the swelling to be an infiltrating lipoma of the tongue. Clinicians should be aware that other causes of tongue swelling may mimic angioedema.