Tumor secreted proteins/peptides (tumor secretome) act as mediators of tumor-host communication in the tumor microenvironment. Therefore, development of anti-cancer drugs targeting secretome may effectively control tumor progression. Novel techniques including a capillary ultrafiltration (CUF) probe and a dermis-based cell-trapped system (DBCTS) linked to a tissue chamber were utilized to sample in vivo secretome from tumor masses and microenvironments. The CUF probe and tissue chamber were evaluated in the context of in vivo secretome sampling. Both techniques have been successfully integrated with mass spectrometry for secretome identification. A secretome containing multiple proteins and peptides can be analyzed by NanoLC-LTQ mass spectrometry, which is specially suited to identifying proteins in a complex mixture. In the future, the establishment of comprehensive proteomes of various host and tumor cells, as well as plasma will help in distinguishing the cellular sources of secretome. Many detection methods have been patented regarding probes and peptide used for identification of tumors.