Cancer vaccines have represented the holy grail of tumor immunology to many. In 2003, there are innumerable approaches to active specific immunotherapy for cancer. The identification of tumor antigens recognized by and able to activate human T-lymphocytes has heightened the enthusiasm for this approach. Melanoma is one of the diseases that has been primarily targeted by vaccine approaches. The identification of peptides and proteins associated with cancer has provided strategies to target specific components of the cancer cell. However, older vaccines utilizing products from whole cells may have a number of advantages. Melacine (Corixa Corp.) is an allogeneic melanoma tumor cell lysate combined with the adjuvant DETOX. Pioneered by Malcolm Mitchell, it has rare but confirmed antitumor activity in metastatic melanoma (5-10%). However, previous analysis of responses in advanced disease and a recent analysis in early-stage adjuvant trials suggest that Melacine may have its greatest benefit in a large subset of melanoma patients who express either the human leukocyte antigen (HLA) class I antigens A2 and/or HLA-C3. This finding must now be confirmed in a large perspective observation-controlled clinical trial to solidify the role of Melacine as an effective cancer vaccine in melanoma.