There is increasing evidence that autoimmunity can inhibit growth of solid tumors. We propose that anti-tumor activity also operates in autoimmunity against hematopoietic stem cells in acquired aplastic anemia (AA). Reduction/dysfunction of regulatory T cells (T(REG)) in AA - rather than being the primary event - could be a response to insufficient or failing anti-tumor reactivity in predisposed individuals, causing elimination of tumor cells and collateral damage to adjacent normal hematopoietic tissue. This pathophysiological mechanism could also apply to otherwise unexplained pancytopenic syndromes which frequently occur in patients with leukemia and lymphoma and non-hematological malignancies. Observations supporting an anti-tumor effect of marrow hypoplasia/aplasia are presented and illustrated with case reports. The conclusion would be that pancytopenia occurring in AA or in AA-like syndromes reflects an ongoing immune reaction against underlying malignancy or infection.