Hepatic arterial infusion chemotherapy (HAIC) for metastatic colonic carcinoma has been associated with gastric ulceration and marked epithelial atypia which may be mistaken for carcinoma. The authors reviewed the gastric histopathologic features of seven patients who developed gastric ulcers following HAIC and compared them with 20 examples of "early" gastric carcinoma. The seven patients had primary colonic carcinomas with hepatic metastases; each had received combination chemotherapy with mitomycin C and 5-fluorouracil via percutaneously placed hepatic arterial catheter. The gastric ulcers became clinically apparent 10 to 45 days after initiation of the final course of HAIC, usually heralded by severe epigastric pain. Based on the authors' observations, histologic features which are indicative of HAIC-associated atypia rather than carcinoma include: preservation of mucosal architecture; atypia accentuated in the basilar gastric glands; bizarre atypia with cellular enlargement exceeding that seen in carcinoma; preservation of a low nuclear-cytoplasmic ratio; cytoplasmic eosinophilia with vacuolization; few or no mitotic figures; cytologic resemblance to radiation effect; similar atypia within fibroblasts and endothelial cells; and absence of intestinal metaplasia in adjacent gastric epithelium.