HOX11, a human homeobox gene with putative oncogenic potential, was originally discovered at the chromosome 10 breakpoint in T-cell acute lymphoblastic leukemias bearing the chromosomal translocation t(10;14)(q24;q11). To provide insight into the possible roles of this gene in development, we isolated and characterized its murine homolog, Tlx-1, and examined its profile of expression. Tlx-1 transcripts are first detected at E8.5 in the surface ectoderm and central mesenchyme of the first branchial arch. This expression subsequently extends to the 2nd, 3rd, and 4th branchial arches, as well as the presumptive pharynx, as these structures develop. Between E12.5 and E15.5, the profile of Tlx-1 expression becomes more complex; expression is observed in the developing pancreas and salivary glands, as well as in several components of the nervous system, including the trigeminal, glossopharyngeal and vestibulocochlear ganglia, the spinal cord, and the curvature of the pons-medulla. In addition, expression is seen in the pinna and external auditory meatus of the outer ear, the tooth primordia, and specific cell populations of the mandible and tongue. These complex patterns of expression are consistent with multiple and varied roles for Tlx-1 in development and suggest that Tlx-1 marks, amongst other cell populations, structures derived from cranial neural crest cells and migratory paraxial mesoderm that arise at corresponding levels along the rostral-caudal axis of the developing embryo.