Dual or multiple cell populations, induced by chimeras, have been the subject of many studies. This long-standing fascination with chimeras has revealed a good deal of knowledge about human inheritance. Although historically most chimeras were caused by natural events, certain current medical intervention therapies are increasing the number of situations that can lead to a mixed cell population, that is, the chimeric condition, in humans. Medical therapies such as transfusion, stem cell transplantation, kidney transplantation, and artificial insemination induce temporary and sometimes permanent chimeras. Such natural or therapeutically induced presentations of chimerism can present challenging issues to the clinical immunohematology laboratory with regard to interpretation of results and subsequent patient management. The purpose of this review was to highlight some of these chimeric states and hypothesize how testing DNA from various tissues can cause apparent discrepancies between phenotype and genotype results.