Comparative immunology has been revitalized by the integration of genomics approaches, which allow a foothold into addressing problems that previously had been difficult to study. One such problem had been the enigmatic finding of overt immune anatomical structures in the lamprey, yet its apparent lack of bona fide immunoglobulin or T cell receptor molecules. The genomic characterization of a novel extended locus that undergoes rearrangements to generate receptor diversity and the subsequent implementation of this diversity in the immune system of lampreys have generated considerable interest as well as new avenues for investigation. Here, we review the anatomical structures of the lamprey that exhibit lympho-hematopoietic characteristics, with the ultimate goal of reconciling these data with contemporary molecular findings. By integrating these datasets we seek to better understand how an alternative adaptive immune system could have evolved.