This article provides a broad overview of the field of inappropriate gene expression in many organisms across the animal and plant kingdoms as well as its importance to human disease in general and cancer in particular. Study of the topic is especially important for understanding how the chaotic maelstrom of evolving and cascading regulatory genetic interactions in an advancing cancer produces its clinical effects and for designing pragmatic solutions to how such disorder might eventually be tamed. It is emphasized that the topic warrants much more attention in research and in clinical practice because of the added value it brings to refining cancer diagnosis and treatment and to the assessment of prognostic markers. It is also particularly relevant to understanding the etiology and extensive clinical manifestations of paraneoplastic syndromes affecting multiple organs remote from the tumor and the treatment or amelioration of the substantial morbidity that they cause in cancer patients. More broadly, inappropriate expression can be caused by a number of mechanisms including mutations, rearrangements of the genome, and viral insertions and, under prolonged selection pressures, also has the potential to be an agent of evolutionary change.