All living systems contain naturally occurring nanoparticles with unique structural, biochemical and mechanical characteristics. Specifically, human saliva exosomes secreted by normal cells into saliva via exocytosis, are novel biomarkers showing tumor-antigen enrichment during oral cancer. Here we show the substructure of single human saliva exosomes, using a new ultra sensitive low force Atomic Force Microscopy (AFM) exhibiting sub-structural organization unresolvable in Electron Microscopy. We correlate the data with Field Emission Scanning Electron Microscopy (FESEM) and AFM images to interpret the nanoscale structures of exosomes under varying forces. Single exosomes reveal reversible mechanical deformation displaying distinct elastic, 70-100nm tri-lobed membrane with sub-structures carrying specific trans-membrane receptors. Further, we imaged and investigated, using force spectroscopy with antiCD63 IgG functionalized AFM tips, highly specific and sensitive detection of antigenCD63, potentially useful cancer markers on individual exosomes. The quantitative nanoscale morphological, biomechanical and surface biomolecular properties of single saliva exosomes, are critical for the applications of exosomes for cancer diagnosis and as a model for developing new cell delivery systems.