Single cell embryo biopsy is a useful but invasive technique for preimplantation diagnosis. Biopsy may be performed by physical (direct zona puncture) or chemical methods (zona drilling with acid solution). This study has analysed the safety of a physical method of embryo biopsy in the mouse. Six adult mice (male and female), three from biopsied embryos and three from a control group (non-biopsied) were subjected to histopathological analyses. Macroscopically, the anatomy and morphology of the internal organs in both groups were normal. Microscopic analyses of 15 major organs, which included the brain, heart, lung, liver, kidney, stomach, intestine, voluntary muscle, spleen, pancreas, adrenal, thymus, skin, testis (male) and ovary (female), in both groups were all normal. These results showed that careful single cell embryo biopsy by direct zona puncture performed at the 8-cell embryo stage had no adverse influence on the macroscopic and microscopic structure of the organs. The remaining pluripotential cells of biopsied embryos developed normal microstructure according to the hereditary messages. Ideally, the safety of embryo biopsy requires observation of three stages after embryo biopsy, namely embryonic and fetal development before birth, neonatal assessment and long-term monitoring after birth.