The Molecular Pathology Program of the Spanish National Cancer Research Center (CNIO) performs molecular analyses of human tumors, allowing prediction of the treatment response to commonly used drugs and at the same time permitting the identification of relevant cancer genes. Biological therapy has so far been based on the study of unique genes or proteins, such as the administration of tamoxifen to endoplasmic reticulum positive tumors, Herceptin for cancer arising from overexpression of c-erb-B2, Cetuximab for cancers associated with overexpressed epidermal growth factor, Rituximab in CD20-positive lymphomas or RAR in progressive multifocal leukoencephalopathy. Although such biologically oriented treatment is making significant progress against different tumor types, it ignores the fact that cancer is a social and multigenic disease. The more common forms of cancer are the result of complex genetic alterations that allow the tumor cells to develop multiple capacities, such as tissue invasion and metastasis, angiogenesis promotion, unlimited replication, apoptosis escape, production of autonomous growth signals, insensitivity to cell cycle control signals and generation of genomic instability. One of the goals of the Molecular Pathology Program is to contribute to an individualized therapeutic strategy, according to the multiple and varied characteristics of the disease. The CNIO is analyzing resistance to commonly used drugs, through molecular study of targets and messenger RNA expression analysis using the microarray technology. The CNIO is also sponsoring the creation of a network of tumor banks in leading hospitals, which will allow massive application of these molecular techniques to large series of patients, diagnosed and treated using standardized protocols. Current projects include the following: (1) A study of the molecular mechanisms of therapeutic failure in cutaneous T-cell lymphoma and malignant melanoma treated with interferon-α, PUVA (a combination of psoralen and long-wave ultraviolet radiation) or both. The objective of this project is to identify the genes involved in interferon-α resistance in myelofibrosis and malignant melanoma. (2) Development of a complementary DNA biochip for the analysis of molecular changes associated with treatment resistance in breast cancer. The CNIO is open to establishing collaborations with other oncology groups to perform integrated analyses of the molecular factors predictive of treatment resistance.