Tissue sampling is useful in differentiating malignant, inflammatory, and infectious processes [C]. Techniques include pinch forceps biopsy, brush cytology, snare excision, and FNA [B]. For malignant lesions, maximal yield is attained with 8 to 10 biopsies [A]. Patients with Barrett's esophagus should undergo systematic biopsy to evaluate for dysplasia [C]. Patients with Barrett's esophagus and high-grade dysplasia should have 4-quadrant biopsies performed every 1 to 2 cm to detect underlying carcinoma [A, B]. Endoscopic mucosal resection may be used to remove malignant or premalignant mucosal lesions [B]. Infectious conditions require multiple biopsies, and if ulcers are present these should be obtained from both the center and edge; brushing and viral culture are adjunctive techniques [B]. H pylori infection can be assessed by gastric biopsy submitted for histologic examination or rapid urease testing [A]. Biopsy of the incisura angularis gives the highest yield for H pylori in untreated patients, but those who have been treated or are taking proton pump inhibitors or antibiotics should have specimens of the corpus and fundus taken as well [A]. Gastric polyps should be extensively sampled or removed when feasible [C]. Gastric polypectomy may carry a higher risk of bleeding than colon polypectomy and postprocedure acid suppressive therapy should be considered [B]. Random biopsies of the small intestine are indicated in the evaluation of diarrheal states, celiac disease, or infections [C]. Duodenal adenomas may be sporadic or associated with familial adenomatosis polyposis and should be sampled or removed when feasible [C]. Colon lesions should be endoscopically excised (polypectomy, EMR) or sampled if lesions are too numerous or removal is not technically feasible [C]. In patients with acute colitis, biopsy may help establish an etiology [B]. Patients with longstanding chronic colitis should undergo systematic surveillance to detect dysplasia, which may indicate an increased risk of cancer [B]. In patients with diarrhea, random biopsy of normal-appearing colonic mucosa may reveal microscopic colitis [B].