An 18-year-old man had a 3-week history of malaise, a 1-week history of a papular eruption, and increasingly severe multisystem neurologic symptoms. A diagnosis of acute monoblastic leukemia was made. Immunophenotypic characterization of peripheral blood, bone marrow, and cutaneous infiltrates revealed a predominant myelomonocytic phenotype with the coexpression of intercellular adhesion molecule type 1, IgE receptor, terminal deoxynucleotidyl transferase, and some T-cell markers. These findings may have important clinical and pathogenetic implications regarding the biologic and pathologic behavior of the myelomonocytic leukemic cells. They also explain in part the impressive presentation of the disease in the skin.