Early chronic myeloid leukemia (CML) and leukemoid reaction (LR) sometimes show similar histological pictures. In order to assess the efficacy of immunohistochemistry in the discrimination of the two forms, twenty bone marrow (BM) trephines of patient with CML and twenty with LR were immunostained and studied. A wide spectrum of antibodies effective on paraffin-embedded tissues (NP 57 anti-neutrophil elastase, Leu M1, MAC 387, KP1, Y2/51, LCA, UCHL1, L26, BerH2 and Glycophorin A) and directed against granulopoietic, erythropoietic, megakaryocytic, monocytic and lymphoid cells was tested by means of the alkaline phosphatase anti-alkaline phosphatase (APAAP) method. Expression of neutrophil elastase in CML and LR showed a different pattern of reactivity in normal and neoplastic granulocytic cells and Y2/51 put in evidence significant discrepancies of megakaryocytes in the two groups. Moreover, a greater number of histiocytic, lymphoid and erythropoietic cells were detected in LR after immunostaining with KP1, LCA, UCHL1, L26 and Glycophorin A. The different immunophenotypical pictures observed, suggest the value of immunohistochemistry as a supplementary diagnostic tool for the differential diagnosis between early CML and LR.