The t(10;14)(q24;q11) chromosomal translocation found in malignant cells of 5–10% of patients with T‐cell acute lymphoblastic leukemia (T‐ALL) involves the T‐cell receptor delta chain gene on chromosome 14 and a breakpoint cluster region on chromosome 10. The candidate proto‐oncogene tcl‐3, thought to be involved in the pathogenesis of t(10;14) T‐ALL, was cloned and found to be elevated in expression in leukemic cells harboring the t(10;14) translocation. Sequence analysis revealed that tcl‐3 is a new homeobox‐containing gene. Comparison of the tcl‐3 cDNA and its 5′ genomic sequences with DNA sequences from the t(10;14) translocation breakpoints showed that this gene is structurally altered in four patients with t(10;14)(q24;q11) T‐ALL. These findings suggest that homeobox‐containing genes that normally act as transcription factors may contribute to T‐cell leukemogenesis when abnormally expressed.