Overall, our findings on ICAM1’s association with patient outcomes as well as its ability to mediate CTC cluster formation and tumor-endothelial cell adhesion through ICAM1-ICAM1 homophilic interactions provide a strong rationale for therapeutic targeting and prognostic evaluation of tumor-intrinsic and -extrinsic ICAM1 in breast cancer metastasis. Here, ICAM1 is linked to neoplasm.