Although Hox genes have been identified as master regulatory genes controlling embryonic development, an alternative view on the role of the Hox gene network suggests that it regulates crucial processes at cellular level in eukaryotic organisms. The Hox network acts at the nuclear cell level as a decoding system for external inductive signals to activate specific genetic programs. Cancer can be considered as an anomalous structure growing inside the human body and following, from an architectural viewpoint, the rules controlling body shape as occurs during embryonic development. As a consequence of this viewpoint, it has been proposed that the whole HOX gene network is involved in controlling phenotype cell identity and three-dimensionality of tissues and organs and, furthermore, that specific HOX genes or groups of genes are implicated in the neoplastic alterations of organs and tissues such as kidney, colon, lung, skin, bladder, breast, prostate. Despite our limited understanding of the mechanisms involved, it has already been possible to identify the specific HOX genes perturbed in certain types of human cancers with greater benefit for cancer patients than for better known oncogenes. Here we foresee the start of clinical trials with the purpose of targeting specific HOX genes in order to achieve a therapeutic effect in cancer patients.