Metastatic spread of cancer is responsible for the vast majority of cancer-related deaths highlighting the need to better understand the cellular mechanisms underlying this phase of cancer, and to monitor disease progression. Our team combines the discovery of a novel circulating tumor cell population, that co-expresses cancer cell and immune cell epitopes (called a hybrid cell), cutting-edge multiplex cyclic immunofluorescence (cyCIF) for interrogation of large panels of proteins on the same tissue section or blood smear, and powerful software (QITissue) that allows for the visualization and analysis of many biomarkers at once. This combination creates a platform that supports non-invasive, real-time monitoring of disease evolution. We set out to determine if disseminated or peripheral blood hybrid cells (called circulating hybrid cells, CHCs) harbored identical expression profiles as tissue-bound hybrid cells.