The identification of tumor antigens has generated a resurgence of interest in immunotherapy for cancer. However, both clinical and animal studies suggest that therapeutic strategies that have mainly focused on the use of CD8+ T cells (and MHC class I-restricted tumor antigens) are not effective in eliminating cancer cells. Recent interest has been directed towards the use of CD4+ T cells in generating antitumor immunity. To this end, the identification of MHC class II-restricted tumor antigens that can stimulate CD4+ T cells might provide opportunities for developing effective cancer vaccines.