Circulating tumor cells (CTCs) are rare tumor cells found in the blood of patients with cancer that can be reliably detected by CTC technologies to provide prognostic, predictive, and diagnostic information. CTC sampling reflects intratumoral and intertumoral heterogeneity better than targeted biopsy. CTC samples are minimally invasive and amenable to repeated sampling, allowing real-time evaluation of tumor in response to therapy-related pressures and possibly early detection. Cytology is the most natural arena for integration of CTC testing. CTC technology may also be deployed to enhance and facilitate the practice of cytology and surgical pathology.