Pearson syndrome (PS) was first described in 1979 like a “new” syndrome of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction (Farruggia et al. 2018). Rotig et al. (1989) first found a deletion of the mitochondrial genome in a patient with PS and assumed that the syndrome was caused by a mitochondrial respiratory enzyme defect. PS belongs to a group of disorders known as mitochondriopathies (Fig. 1). The syndrome is a multisystem mitochondrial disorder characterized by macrocytic sideroblastic anemia to require transfusion support, with or without pancytopenia, exocrine pancreatic dysfunction, and lactic acidosis (Pearson et al. 1979; Rötig et al. 1995). Typically the bone marrow aspirate of affected patients shows the presence of vacuolization in myeloid and erythroid progenitors (Fig. 2). The prevalence of all mitochondrial disease is 1/4300 newborns and 11,5/100.000 in the general population (Chinnery et al. 2000). The incidence of PS is about one case per million with no sex predilection (Farruggia et al. 2018). The disease classically appears during the infancy with bone marrow failure and exocrine pancreatic insufficiency, although several neonatal cases have also been described (Tadiotto et al. 2018). Survival and spontaneous hematological improvement is possible even though 50 percent of affected children die during infancy because of bone marrow failure, sepsis, metabolic acidosis, liver failure, and renal failure.