Although splenic rupture is a recognized complication of primary amyloidosis, very few cases have been reported in the context of stem cell transplantation. A patient with systemic primary amyloidosis with renal and cardiac involvement and factor X deficiency, who developed a splenic rupture 24 h after the peripheral blood stem cells infusion during autologous transplantation, is described. This complication has been reported during stem cell mobilization and after post-transplant hematopoietic recovery, but we have not found a previous report of splenic rupture in the immediate postinfusion period. This case illustrates that splenic rupture can occur at any time during the transplant procedure. Need for close monitoring, particularly in patients with factor X deficiency after receiving granulocyte colony stimulating factor, two recently recognized risk factors for splenic hemorrhage, is highlighted.