We describe the case of a 55-year-old man with scleredema of Buschke of the torso complicated by insulin-dependent diabetes mellitus. Due to (i) the patient's poor general health status, (ii) the similarity between scleroderma and scleredema of Buschke, and (iii) the well known efficacy of factor XIII infusions in scleroderma, we attempted an intravenous treatment with factor XIII. This therapy resulted in marked increase of movements and in softening of the skin, together with ultrasonographic and histopathological improvements. In conclusion, to the best of our knowledge, this is the first case in which factor XIII has been successfully used for the treatment of scleredema of Buschke.