Low-grade lesions of graft-versus-host disease (GVHD) in the colon are not uncommon. To determine if minimal diagnostic criteria can be established in such biopsies, we correlated histologic findings with clinical history and investigated the role of endoscopy and electron microscopy in establishing GVHD. About 85 colonic biopsies that were histologically consistent with GVHD from 47 bone-marrow transplant recipients were reviewed retrospectively. Of nine cases showing only a single apoptotic cell in the intestinal epithelium, only four lacked any confounding factors of GVHD. These cases, while too few to assess the utility of finding one apoptotic cell with statistical significance, appear to support the idea that in the appropriate clinical setting, a single apoptotic cell could be reported as possibly representing early GVHD. Endoscopic findings did not reliably correlate with histology. Although electron microscopy can be a useful adjunct, it does not contribute to the diagnosis of GVHD.