In patients with systemic sclerosis (SSc) treatment-related mortality after autologous stem cell transplantation (ASCT) appears to be increased as compared to patients with hematological malignancies. In our phase I/II study on ASCT in autoimmune diseases a patient with SSc died on day 2 after ASCT. Here we report the results of the autopsy which revealed advanced pulmonary and cardiac fibrosis as the most probable cause of death. In spite of detailed technical examination before enrollment, the cardiopulmonary function tests did not reflect the advanced stage of the disease. We conclude that in selected patients with SSc, biopsies should be performed to reduce mortality after ASCT.