Management of metastatic breast cancer is critical to maximizing survival with good quality of life. Circulating tumor cell (CTC) levels in the peripheral blood hold promise for enabling improved patient care. We describe a case of a 47-year-old female with infiltrating ductal carcinoma who developed metastatic disease. Serum tumor markers were discordant with imaging studies at several time points. CTC levels were used to support decision making in light of the discordant data. The use of this tool enabled prompt changes in therapy with progressive disease and supported suspending therapy to enable recovery from treatment adverse effects when a significant response was detected by imaging and CTCs were absent from the peripheral circulation. The additional information provided by CTC enumeration helped clarify disease status and provided support for treatment decisions.