Lipopeliosis is an unusual liver lesion in which sinusoids become engorged by fat globules. It arises in newly transplanted donor livers that display varying degrees of fatty change. If, after transplantation, hepatocyte necrosis secondary to ischemic or preservation injury occurs, the fat escaping the hepatocytes becomes sequestered in the sinusoidal spaces. We previously described this lesion in a case report; we now describe four more cases to define better the incidence, immunohistochemical features, and clinical spectrum. Of 101 transplanted livers, the lesion was noted in five of 28 (18%), with both preservation injury and mild to moderate fatty change present 1 week following transplantation. Factor VIII-related antigen, collagen IV immunoperoxidase, and oil red O stains confirmed the engorgement of sinusoids by fat droplets, and a stain for CD68-positive cells identified a macrophage reaction around the fat droplets. The patient in our original report developed severe graft dysfunction with residual scarring of the centrilobular zone. Two of the four additional cases had no residual side effects from the lipopeliosis; however, two cases were associated with loss of graft. We conclude that lipopeliosis may be fairly common (5% of transplants). Its clinical outcome can vary greatly and most probably depends on the extent of hepatocellular necrosis.