Exosomes are 30-100 nm sized membrane vesicles released by cells into extracellular space and mediate the intercellular communication via transfer of proteins and RNAs. To better understand the function of these microvesicles in lung carcinogenesis, we employed a Triple SILAC quantitative proteomic strategy to examine the differential protein abundance between exosomes derived from an immortalized normal bronchial epithelial cell line and two non-small cell lung cancer (NSCLC) cell lines harboring distinct activating mutations in the cell signaling molecules Kirsten rat sarcoma viral oncogene homolog (KRAS) or epidermal growth factor receptor (EGFR). We were able to quantify 727 exosomal proteins derived from the three cell lines. Proteins associated with signal transduction are enriched in NSCLC exosomes which are functionally active in regulating cell proliferation. The study is the first to investigate protein abundance differences in exosomes derived from NSCLC cells and their normal counterparts, and reveals the role of exosomes in NSCLC cancer progression, which may have clinical implications in biomarker development for patients with NSCLC.