Cancer metastases develop when tumor cells known as circulating tumor cells (CTCs) are shed from a tumor, circulate through the blood stream and colonize a distant tissue. The number of CTCs detected in a metastatic breast cancer patient is currently used as an independent predictor of outcome and for serial monitoring of treatment response. There are many methods currently being developed to detect, capture, and analyze CTCs. Most methods including the only FDA-cleared method (CellSearch) are based on the detection of epithelial markers on the surface of CTCs. However, 40% of patients with metastatic breast cancer have no detectable CTCs using these criteria. The objective of this project was to develop a method to identify and define CTC subtypes (phenotypes) based on surface markers. The novel identification and subtyping we propose will improve the currently used clinical diagnostic which only enumerates CTCs with an epithelial phenotype. Our proposed method will detect a more comprehensive set of CTCs and determine a patients unique CTC subtype profile associated with a specific cancer outcome. Our strategy is to use a combination of antibodies to devise a subtyping schema capable of differentiating potential subtypes. We have tested this approach by using a library of antibodies to detect a panel of breast cancer cell lines including 4 different molecular categories of breast cancer cell lines: MCF-7 (luminal); MDA-MB-231 (mesenchymal-like); HCC1954 (basal A); and, SK-Br-3 (HER2). Our data indicates that we are able to subtype each of these 4 cell lines and provides preliminary evidence that this approach holds promise for identifying and subtyping heterogeneous circulating breast cancer cells. The ability to subtype CTCs will provide a non-invasive method to predict specific cancer outcomes such as metastatic potential, the location of organ-specific metastasis, dormancy versus non-dormancy, as well as to monitor treatment. The ability to predict future organ-specific metastases will greatly improve personalized treatment regimens and prevent the development of metastatic cancer.