The physiology of the immune system involves morphologic and functional changes occurring along ageing, with a decrease in immune response and an increase in autoimmune phenomena, even in the absence of overt disese. Autoimmune cytopenias, namely autoimmune hemolytic anemia (AIHA), chronic idiopathic neutropenia (CIN) and aplastic anemia (AA), show different epidemiologic predilection, but are increasingly diagnosed in the elderly, where complications and comorbidities are more frequent. A systematic review of recent literature, shows that comorbidities as well as underlying deficiencies, medications, neoplasms, and, pathophysiologic chronic organ failures, frequently challenge the differential diagnosis in this setting and should always be evaluated and excluded.