Conjoined twinning is a very rare congenital disorder that results from partial separation during the development of the embryos in cases of monozygotic twins. Male-female symmetrical conjoined twins with an opposite phenotype in relation to their biological sex are an extremely rare developmental abnormality due to the complications involved, from an embryological, genetic, hormonal, clinical, and ethical standpoint. In this review, we discuss the embryological causes of conjoined twinning, sexual differentiation processes, and the potential causes of discordant phenotypical sex development through chromosomal mosaicism, epigenetics, asymmetry of hormone distribution, or receptors. Furthermore, Disorders of Sex Development (DSD), prenatal diagnosis and molecular analyses, psychosocial impacts, surgery, and ethical issues related to sexual discordance among conjoined twins are evaluated. Our current scientific knowledge is limited since such cases are extremely rare.