In hematological neoplasms CD56 (N-CAM) is expressed by T/natural killer (NK) cell lymphoma, by most neoplastic plasma cells in multiple myeloma and also in a subset of acute myelogenous leukemias (AML). In the latter, it is an indicator of poor clinical outcome. Most of the data on CD56 expression in acute leukemia have been obtained by flow cytometric analysis. Up to now, no systematic analysis of the expression pattern of CD56 in formalin fixed paraffin embedded bone marrow biopsies of acute leukemias has been performed. We immunohistochemically studied the expression of CD56 in a series of 141 bone marrow biopsies fixed in Sublimat Mercury II Chloride (SUSA) including 100 cases of AML FAB M0-M7, 11 cases of AML not further specified, 3 cases of biphenotypical leukemia, 20 cases of acute lymphoblastic leukemia (ALL) and 7 cases of reactive bone marrow biopsies. Overall, 14 of 134 (10%) leukemia cases were positive for CD56. Detail analysis revealed positivity in 5/13 cases of AML M5 (38%), 3/9 AML M1 (33%), 1/8 AML M0 (13%), 1/11 AML not specified (9%), 2/31 AML M2 (7%) and 2/26 AML M4 (8%). All cases of ALL and biphenotypic leukemias were CD56 negative. The CD56 expression in AML M5 was statistically significant (p = 0.003). On paraffin embedded bone marrow biopsies CD56 expression occurs in de novo AML with an overall frequency of 13%. It is significantly correlated with AML M5, which is positive in 38% of the cases. Cases of ALL are consistently CD56 negative.