Mammals are generally held to be exceptions to the rule that organization of the egg plays a role in specifying the differentiation of cells, axes, or other aspects of patterning in the early embryo. However, there are several grounds for questioning this conclusion. Not only do certain experimental findings remain unexplained but, more importantly, nearly all have been interpreted specifically in terms of the differentiation of trophectoderm versus inner cell mass. The possibility that egg organization is instrumental in patterning of the early embryo in mammals has so far been almost entirely neglected, notwithstanding evidence that the mouse blastocyst becomes bilaterally symmetrical before it implants. Difficulties confronting attempts to tackle the issue of the significance of egg organization in mammals are discussed with respect to polarity and cytoplasmic differentiation in the oocyte and zygote. Evidence for an enduring influence of the maternal genome during early development is reviewed and weaknesses in the case against a role for egg organization are exposed. Finally, consideration is given to what needs to be done if this issue is to be resolved.