Transfusion-associated graft-versus-host disease (TA-GVHD) is a relatively rare and interesting entity. Despite a range of pathophysiological and therapeutic approaches, it has a high mortality. It is possible to prevent the disease by prophylaxis only. It is possible to miss the entity in routine clinical practice and reach a different diagnosis due to its non-specific signs and symptoms. Four patients with signs and symptoms suggestive of TA-GVHD were evaluated and the literature reviewed. The transfusion history was of great importance, as was the exclusion of other conditions that may present with similar signs and symptoms (fever, skin rash, diarrhea, pancytopenia, icterus and renal failure). Confirmation of TA-GVHD was by skin biopsy. TA-GVHD must be considered as a differential diagnosis in patients who present with fever, pancytopenia, diarrhea, skin rash and icterus, and the transfusion history must be questioned. Mortality is very high despite various therapeutic approaches. This makes prophylaxis essential. TA-GVHD can be prevented by irradiation of blood products and by avoiding the use of blood transfusions from family donors.