Cryptococcal infection of the gastrointestinal (GI) tract is rarely reported, either in disseminated disease or as an isolated finding. We report a case of gastric cryptococcal infection diagnosed by endoscopic biopsy as the initial presentation of the acquired immunodeficiency syndrome (AIDS), and an additional seven cases found by reviewing 23 other autopsy cases of disseminated or pulmonary cryptococcal infection. The patient with gastric cryptococcosis was a 38-year-old man who presented with symptoms of gastroesophageal reflux including odynophagia. Upper GI endoscopy showed Candida esophagitis and gastric nodules. Biopsy of the nodules revealed cryptococcal infection and granulomatous inflammation of the fundic mucosa and submucosa. The patient died 3 weeks later despite anti-fungal therapy. Autopsy revealed widespread cryptococcal infection involving the cecum but not the stomach, suggesting that the gastric lesions resolved with therapy. The sites of infection in the seven other cases were esophagus (three), stomach (one), terminal ileum (one), colon (three), gallbladder (one), and in a focus of Kaposi's sarcoma in the wall of the small bowel (one). Esophageal candidiasis was also present in two of the cases of esophageal cryptococcal infection. Predisposing factors were AIDS (3), hematologic malignancy (3), and corticosteroid therapy (1). In summary, we report a case of gastric cryptococcosis and conclude that cryptococcal infection involves the GI tract more commonly than has been previously reported, with 8/24 (33%) cases positive in our autopsy series. Of clinical significance is the observation that GI cryptococcal infection may be the initial presentation of disseminated disease in the immunocompromised patient, and cryptococcal infection of the esophagus may be found in the setting of esophageal candidiasis.