False-positive and false-negative diagnoses of cancer seldom occur during evaluation of gastric mucosal biopsy specimens obtained during flexible fiberoptic endoscopy of the stomach. When they do occur, false-negative diagnoses are usually the result of undersampling of the lesion, whereas false-positive diagnoses are the result of overinterpretation of benign histologic lesions. The diagnosis of diffuse signet ring cell adenocarcinoma is associated with both false-positive and false-negative diagnoses of cancer. The signet ring cell can be easily overlooked. Mucicarminophilic cells can be overinterpreted as diffuse signet ring cell adenocarcinoma. Polyvinylpyrrolidone is an unusual cause of this type of false-positive diagnosis of gastric adenocarcinoma. Judicious use of histochemical stains, immunohistochemistry, and electron microscopy plays a significant role in avoiding the false-positive diagnosis of diffuse signet ring cell adenocarcinoma. The authors wish to acknowledge the diagnostic assistance provided by Dr Jan Kennedy, Department of Pathology, Grady Memorial Hospital; Dr Robert Pascal, Department of Pathology, Emory University; Dr Henry Appelman, Department of Pathology, University of Michigan Hospitals; Dr Frank B. Johnson, Chief, Chemical Pathology at the Armed Forces Institute of Pathology, Washington, DC, and Dr Leslie H. Sobin, Chief, Gastrointestinal Pathology at the Armed Forces Institute of Pathology, Washington, DC. © 1994 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.