Optimal management of therapy can improve quality of life, and potentially survival, of patients with metastatic prostate cancer. Circulating tumor cell (CTC) enumeration in the peripheral blood holds promise for facilitating optimal therapy management based on high cancer specificity and prompt response to changes in disease status. We present the case of a 54-year-old male diagnosed with metastatic prostate cancer. The patient's disease status was monitored radiographically and by serial determinations of serum prostate-specific antigen concentration, performance status, and CTC enumeration. At multiple visits, the disease status was not clear due to discordance between standard assessments. The additional information provided by CTC enumeration helped clarify disease status and provided support for treatment decisions.