Even though the diagnostic and prognostic value of circulating tumor cells (CTCs) have been demonstrated, their clinical utility and widespread adoption have been limited. Herein, we describe a new device, Size Dictated Immunocapture Chip (SDI-Chip), for efficient, sensitive and spatially resolved capture and detection of CTCs. SDI-Chip enables selective, frequent and extended interaction of CTCs with hydrodynamically optimized immunocoated micropillar surfaces. CTCs with different antigen expression levels can be efficiently captured and spatially resolved around the micropillars. Capture efficiency greater than 92% with a purity of 82% was achieved with blood samples. CTCs were detected in non-metastasis colorectal (CRC) patients, while none was detected from healthy volunteers. We believe that SDI-Chip will facilitate the transition of tumor diagnosis from anatomical pathology to molecular pathology in localized CRC patients.