Although phenotypic heterogeneity of childhood T-cell acute lymphocytic leukemia (T-ALL) which bear receptors for sheep red blood cells (E-rosettes) and/or T-cell-associated antigens has been reported, there are certain clinical features which are shared by most patients. A mediastinal mass is one of the most characteristic presentations in this particular disorder. This report describes four children with ALL, who presented with a mediastinal mass. Three patients were E-rosette-negative and one was E-rosette-positive. Individual surface phenotypes, defined by a panel of monoclonal antibodies, were quite different. Since Ig gene organization is an essential property of cells of B-lineage, it was surprising to find that analysis of genomic DNA revealed immunoglobulin (Ig) gene rearrangements in two of them. These findings suggest that there is significant heterogeneity even among those leukemias associated with a mediastinal mass, and that a mediastinal mass may not clearly indicate origin from cells of T-lineage. This heterogeneity may reflect differences in leukemogenesis and may have prognostic and therapeutic implications.