A 9‐month‐old infant presented with hypercalcemia and lytic bone lesions. Suspicion for malignancy led to a bone marrow examination, which showed replacement of the marrow by a small round blue cell infiltrate. Flow cytometric analysis of these cells showed an unusual immunophenotype in that these cells were dim CD45, HLA‐DR, and CD10 positive, but CD19, CD20, CD79a, and CD34 negative. Southern blotting showed clonal rearrangement of immunoglobulin heavy chain (IgH) which confirmed a diagnosis of precursor B acute lymphoblastic leukemia (ALL). He received supportive treatment with hydration and pamidronate, but had recurrent episodes of hypercalcemia. Once the correct diagnosis of ALL was established, the patient was treated with an infantile ALL chemotherapeutic regimen and the hypercalcemia resolved. This case highlights the usefulness of immunoglobulin gene rearrangement studies in atypical cases of ALL. © 2004 Wiley‐Liss, Inc.