This presentation will provide the framework for addressing the challenging problems of cancer among people with severe and persistent mental illness (SMI). Worldwide, studies demonstrate the many challenges, consequences and complications including not receiving proper cancer screening, prevention and suboptimal or delayed cancer treatment and reduction in years of life expectancy compared to the general population. Review of the literature, citing some of the most significant papers regarding the areas of cancer screening and prevention, incidence, mortality, and palliative care in SMI. Definitions for SMI, worldwide prevalence, problems at work, stigma and discrimination, inequalities in cancer care and outcomes, impact on person’s and family’s quality of life and increased physical problems will be provided. Additionally, end-of-life care has been shown to be lacking for those with SMI, including lower levels of physical, psychological, and spiritual care. To grasp the magnitude of the problem, data from studies of people with SMI will be provided showing reduced rates of screening, less access to behavioral intervention and prevention, fragmentation of mental health care and cancer care, poorer or suboptimal treatment. In the palliative care setting, people with SMI, compared to the general population, are less likely to be prescribed analgesics, less likely to receive palliative care, more likely to die in nursing homes, and less likely to access community-based specialty palliative care. The role of stigma and access to care, problems related to consent and capacity and better practices for pharmacology, psychosocial interventions, communication, collaboration, and education will be highlighted. Importantly, Psycho-oncology has a clear and significant role in helping to improve the disparities in this vulnerable population regarding screening and treatment for cancer and optimizing the provision of treatment after diagnosis. This presentation is a call to action.