Development of the posterior neural tube (PNT) in human embryos is a complicated process that involves both primary and secondary neurulation. Recently, we histologically examined 20 human embryos around the stage of posterior neuropore closure and found that the axially condensed mesenchyme (AM) intervened between the neural plate/tube and the notochord in the junctional region of the primary and secondary neural tubes. The AM appeared to be incorporated into the most ventral part of the primary neural tube, and no cavity was observed in the AM. In this study, we report three cases of human embryos with myeloschisis in which the open primary neural tube and the closed secondary neural tube overlap dorsoventrally. In all three cases, part of the closed neural tube was located ventrally to the open neural tube in the lumbosacral region. The open and closed neural tubes appeared to be part of the primary and the AM-derived secondary neural tubes, respectively. Thus, these findings suggest that, in those embryos with myeloschisis, the AM may not be incorporated into the ventral part of the primary neural tube but aberrantly differentiate into the secondary neural tube containing cavities, leading to dorsoventral overlapping of the primary and secondary neural tubes. The aberrant differentiation of the AM in embryos with lumbosacral myeloschisis suggests that the AM plays some roles in normal as well as abnormal development of the human posterior neural tube.