Circulating tumor cells (CTCs) obtained noninvasively can be used as a surrogate for primary tumor cells.Indeed,CTCs are likely derived from clones in the primary tumor, suggesting that they can be used for all biological tests applying to the primary cells they represent.Several methods have been developed isolate CTCs in the peripheral blood of patients with cancer.Such methods rely mainly on cytometric/immunological characteristics, although CTCs may also be isolated by size.Any useful method for isolation of CTCs must allow their: (i) identification and enumeration;(ii) characterization through immunocytochemistry, fluorescence in situ hybridization (FISH) assays and molecular techniques using optimal quality DNA/RNA.Isolation of an adequate number of CTCs in a reproducible manner and their use for molecular studies has been limited due to their extreme rarity (around 1 per 109 cells in peripheral blood of patients with metastatic cancer) and methodological limitations.Furthermore, CTCs must be isolated alive for testing their potential capacity to initiate tumor formation in animal models and must become easily accessible to a large range of molecular biological analysis.We describe a newly developed filtration minidevice, the ScreenCell(R),which can isolate, quantify, and analyze circulating tumor cells from a blood sample.In the ScreenCell(R) device, blood flow passes through a microporous membrane filter allowing size-selective isolation of CTCs under fully reproducible and standardized conditions.The ScreenCell(R) device has been designed with the aim of achieving isolation of tumor cells without the requirement for large and expensive apparatus.Furthermore, CTCs isolated onto the filter can be analyzed using all relevant cellular and molecular biological techniques pertinent to the identification and characterization of CTCs and their potential genetic abnormalities.The device allows formalin-fixed paraffin-embedded CTCs sections opening access to extended biomarkers analysis of each isolated cell.The device can isolate living cells, allowing further tissue culture experiments.Furthermore, tumor cells can be isolated without using an antibody-based assay which may not capture microemboli and cells undergoing epithelial-mesenchymal transition (EMT) which is considered to be a crucial event in the metastatic process.Finally, our results show that the ScreenCell(R) device can be used for the isolation of a large spectrum of tumor cells, including cells of non-epithelial origin.