In this study, we developed a novel strategy integrating subtraction enrichment and immunostaining-FISH (SE-i•FISH®), which enables effective depletion of WBCs and non-hemolytic removal of RBCs, to establish an expeditious detection of non-hypotonic damaged and non-hematopoietic aneuploid CTCs regardless of CK or EpCAM expression and size variation ranging from similar or smaller than WBCs up to larger tumor cells [5, 28, 29]. Here, EPCAM is linked to neoplasm.