Colchicine is an alkaloid with antimitotic ability used to treat a variety of medical conditions. Colchicine toxicity can result in multiorgan failure and death. The histopathologic features of colchicine toxicity in gastrointestinal biopsies have not been reported. Twenty-one gastrointestinal mucosal biopsies obtained from nine patients receiving oral colchicine therapy were studied. Immunohistochemical staining for Ki67 proliferation antigen was performed, and medical records of each patient were reviewed. All patients had a history of gout. Four patients with chronic renal failure also had clinical evidence of colchicine toxicity, and the other five patients did not. Distinct morphologic changes, seen as metaphase mitoses, epithelial pseudostratification, and loss of polarity, were seen in biopsy material from 4 of 4 (100%) patients with clinical colchicine toxicity. Three of these four cases (75%) also contained abundant crypt apoptotic bodies. These morphologic features were best seen in the biopsies from duodenum and gastric antrum, with relative sparing of the gastric body in the upper gastrointestinal tract. Ki67 staining demonstrated an expansion of the proliferating region in three available cases with clinical colchicine toxicity. These distinctive morphologic features were not seen in the five patients without clinical colchicine toxicity. These results indicate that colchicine toxicity can produce diagnostic morphologic features in gastrointestinal mucosal biopsies. Recognition of these features is important because colchicine toxicity can be fatal if undiagnosed clinically.