Small cell lung cancer (SCLC) is characterized by early dissemination through the blood system with the majority of patients succumbing to their disease in 9-11 months. Despite evaluation of multiple new agents a platinum doublet has remained the standard of care for over 25 years. We believe that the lack of understanding of the biology of SCLC has contributed to our failure to advance treatment and prolong survival. Tumor and blood biomarkers have been shown to be a powerful tool for increasing our understanding of the complex biology of cancer and determining prognosis and response to therapies. Currently, there are no validated biomarkers for response or to follow disease activity in SCLC. Detection of Circulating Tumor Cells (CTCs) is a laboratory technique that became available in the last few decades. Newer, more sensitive technology for the isolation and characterization of CTCs using a rare event imaging system with automated fluorescence microscopy known as CellSearch has demonstrated value in several cancers. CTCs detection by this system is approved as a prognostic biomarker in metastatic breast cancer, and as a tool to monitor disease in metastatic colorectal cancer and castrate resistant prostate cancer.