Hypoplastic myelodysplastic syndromes (h-MDSs) are difficult to distinguish from acquired aplastic anemia (AA) because of the considerable clinical, cytologic, and histologic similarities between these two disorders. Recent studies have suggested that the bone marrow (BM) in AA is characterized by a decreased number of CD34+ cells and reduced expression of proliferating cell nuclear antigen (PCNA), features that have not been associated with MDS. To determine the potential importance of these markers in the differential diagnosis of hypoplastic BM disorders, we immunostained 50 BM biopsy specimens of cytogenetically characterized cases of AA (27) and h-MDS (23). Immunohistochemical staining for CD34 was performed with QBEND10 (Vector, Burlingame, Calif), a monoclonal antibody (MoAb) reactive in routinely processed specimens, while PCNA was assessed by the PC10 MoAb (Dako, Carpinteria, Calif) using a microwave over-based antigen retrieval technique. Bone marrow specimens of h-MDS cases showed statistically higher values of PCNA and CD34 than did those of the AA cases: mean values (+/- SD) of CD34-positive cells in h-MDS, 0.94% +/- 1.1; AA, 0.04% +/- 0.1 (P = .0002); PCNA-positive cells in h-MDS, 43.59% +/- 13.3; AA, 14.80% +/- 6.4 (P < .0001). Our study confirms that AA is characterized by low expression of PCNA in BM and reduced CD34 frequency compared with h-MDS and supports the concept of an early deficiency of stem cells in the former disorder. The results also illustrate how immunostaining permits a simple distinction of these conditions in routinely processed BM biopsy specimens.