In an effort to improve working conditions in the histopathologic laboratory, we have investigated whether less toxic substances may be substituted for the toxic organic solvent xylene currently in use. Xylene is used in the clearing as well as the deparaffinization process. We have tested whether the substitution of xylene by olive oil and coconut oil leads to any difference in the quality of the histologic sections. Two tissue blocks from each of 232 specimens sent for histopathologic evaluation were subjected to parallel processing in xylene and oil. The specimens represented a broad spectrum of tissue types. All sections were stained with hematoxylin‐eosin to permit evaluation of histologic and cytologic details. Furthermore, a range of histochemical and immunohistochemical stainings were applied to a subgroup of tissue sections. The results showed qualitative differences between xylene‐processed and oil‐processed tissue in only a minority of cases. In no cases were the oil‐processed samples considered less suitable for histologic diagnosis. In the histochemical and immunohistochemical stainings, no differences were registered. Although the long‐term stability of oil‐processed tissue remains to be clarified, we conclude that less toxic vegetable oil may probably be substituted for xylene without losing valuable diagnostic information.