The stroma surrounding many malignant tumors resembles granulation tissue. To test the hypothesis that such stroma stimulates tumor invasiveness, we compared, by electron microscopy and immunohistochemistry, the growth patterns of CC531 rat colon adenocarcinoma in 2 experimental situations: (i) after transplantation into the undisturbed subcutaneous connective tissue of rats, and (ii) after transplantation into experimentally induced subcutaneous granulation tissue in rats. For the latter experimental situation, a subcutaneous "tissue chamber" was designed allowing fragments of tumor tissue to be transplanted into the very center of developing granulation tissue. In the undisturbed subcutaneous tissue, the whole tumor was generally encapsulated, and the tumor cells were arranged in compact groups with a strong tendency to form acini. In the pre-formed granulation tissue, on the other hand, the tumor tissue closely matched descriptions of invasive colon carcinomas in the literature and met the criteria for the "invasive morphotype". In this situation, the tumor consisted of thin, unorganized, widely dispersed strands of irregular tumor cells with numerous protrusions that deeply penetrated the surrounding matrix. Our results show that an invasive morphotype can be evoked by pre-inducing granulation tissue at the transplantation site.