Most tumors, including prostate carcinoma, are heterogeneous mixtures of neoplastic cells and supporting stromal matrix. Attempts to vaccinate as a means to treat or prevent cancer have typically relied on use of a single antigen or cell type. In the case of whole-cell vaccines, clonal populations of cancer cells are grown in culture and harvested for vaccine material. However, it is clear from microarray data that neoplastic cells grown in culture are greatly different from those found in vivo. Tissue vaccines are harvested directly from tumors and are used to immunize the animal or the patient. They are antigenically rich, in that they are comprised of not only neoplastic cells but also supporting stromal matrix; furthermore, they include antigens that may be expressed only in vivo and which may be critical to a successful immune response to the cancer. For these reasons, the idea that tissue vaccines for cancer have potentially great utility has merit and should be explored further.