A device for Computer Simulated Marking Targeting Biopsy (CSMTB) has at least a space locator, and a main control module, including a surface model sub-module, a positioning sub-module, a tracking sub-module, a virtual endoscope sub-module, and a marking targeting biopsy sub-module. The device accurately detects minimal gastric lesions, and reduces pain to patients and thus decreases the workload of a doctor.