HS is the most frequent congenital hemolytic anemia in Caucasians, with reported prevalence ranging from 1:2,000 to 1:5,000, and is characterized by a highly heterogeneous molecular defect, involving the genes coding for RBC membrane proteins SPTA1 (α-spectrin), SPTB (β- spectrin), SLC4A1 (band 3), ANK1 (ankyrin), EPB42 (protein 4.2). Here, SPTA1 is linked to histiocytic sarcoma.