Well-established solid tumors (at least 14 days old and >1cm in average diameter) are extremely difficult to eradicate immunologically in mice. Most cancer patients that seek medical attention bear primary or metastatic tumors that have grown for longer and that are larger than the tumors we call established. Therefore, focusing research on the problems of rejecting well-established mouse tumors might help in the development of novel concepts and protocols for destroying tumors in patients. A particular problem with established cancers is that even when treatments induce temporary regression, cancer often recurs. Recent studies suggest that manipulation of the stromal microenvironment of these tumors can induce immune recognition and regression. Furthermore, targeting cancer cells as well as tumor stroma for immune destruction might be needed to prevent recurrence.