Macroglossia is an uncommon condition that causes cosmetic and functional disabilities. We present a case of a 67-year-old patient with the past medical history of vitamin B12 deficiencies who presented with macroglossia and was found to have amyloidosis. She had an enlarged tongue with multiple ulcerations secondary to traumatic injury from dentation along with difficulty swallowing. Laboratory workup was unremarkable apart from elevated C reactive protein (CRP) and low complement 3 (C3) levels. On the second day of admission she had gastrointestinal bleed; computed tomography (CT) scan of the abdomen with oral contrast was performed which revealed nodular thickening of the stomach suspicious for gastric malignancy. Endoscopy was postponed as there was concern that macroglossia could comprise the airway. A biopsy of the tongue was performed and histological staining was positive suggestive of the amyloidosis. We discuss here the probable underlying causes of macroglossia and amyloidosis.