Acute lymphocytic leukemia with mature B-cell phenotype (B-ALL) is a rare type of ALL. Although B-ALL cells commonly have a characteristic chromosomal translocation that includes 8q24 (the location of the c-myc protooncogene), the leukemic cells of the two patients reported in this paper showed normal karyotypes. This finding was confirmed by Southern blot analysis of bone marrow cells in case 1. A c-myc probe was used, and no rearrangement or amplification of c-myc expression was found; B-ALL with the translocation including 8q24 is reported to show high levels of expression of rearranged c-myc. Investigation of anti-Epstein-Barr virus (EBV) antibody revealed that both cases 1 and 2 had a past history of EBV infection. However, at least in case 1, integration of the EBV genomic DNA into the leukemic cells was not detected by the polymerase chain reaction in which specific primers for EBV were employed. The difference in pathophysiology between B-ALL with and without the 8q24 translocation is unclear, however, the prognosis of the two patients with B-ALL with the normal karyotype was as poor as that of B-ALL with the chromosomal translocation.