Early detection of small cell lung cancer crucially demands highly reliable markers. Growing evidence suggests that extracellular vesicles carry tumor cell-specific cargo suitable as protein markers in cancer. Therefore, we isolated plasma-derived microvesicles from newly diagnosed small cell lung cancer patients and investigated proteome dynamics of these microvesicles aiming at improving the detection of small cell lung cancer. A total of 1,223 proteins were initially identified. After data processing and statistical analysis, several proteins were found to be differentially expressed in comparing small cell lung cancer patients and healthy individuals. Furthermore, our data may indicate involvement of complement activation, integrin-mediated signaling, cell adhesion- and migration, and blood coagulation in small cell lung cancer pathogenesis.