The Shwachman-Diamond syndrome (SDS) is a rare congenital disorder for which inheritance by an autosomal recessive trait has been suggested. Shwachman-Diamond syndrome is defined by exocrine pancreatic insufficiency combined with severe neutropenia. Moreover, SDS patients are at risk to develop neoplastic hematologic diseases. We describe 2 SDS-affected daughters of consanguine parents who were born 1 year apart, at 35 and 36 weeks of gestation, and who died at the age of 4 and 3.5 months, respectively, due to respiratory infections. Histologic bone marrow evaluation of the second-born child revealed a diffuse proliferation of immature B cells, which comprised 40% of the total cellularity. These cells were identified as precursor B cells by immunophenotyping studies (CD79a(+)/CD10(+)/CD20(-)/CD22(-)/CD34(-)/ terminal deoxynucleotidyl transferase(-)). Molecular determination of the immunoglobulin heavy-chain gene status did not reveal clonality. The emergence of this peculiar B-cell population was interpreted as a marked increase of hematogones. Although the clinical significance and the exact function of hematogones is still obscure, they may play a critical regenerative role in the regulation of hemopoiesis, but without malignant potential in SDS. Immunophenotyping and molecular studies, therefore, have potential value in the differential diagnosis of primary bone marrow failures. This report adds SDS to the spectrum of conditions in which a prominent number of hematogones may be observed.