Platelets play an important role in tumor growth and at the same time, platelet characteristics are affected by cancer presence. Therefore, we investigated whether the platelet proteome can be used as a source for biomarkers of early-stage cancer. Patients with early-stage lung (n=8) and head of pancreas cancer (n=4) were included, as were healthy sex- and age-matched controls for each subgroup. Blood samples were collected from controls and from patients before surgery. Furthermore, from six of the patients, a second sample was collected two months after surgery. NanoLC-MS/MS-based proteomics was used to quantify and compare the platelet proteome of patients to controls. Also, samples before surgery and after surgery were compared. Analysis revealed that the platelet proteome of patients with early-stage cancer is altered as compared to controls. In addition, the platelet proteome changed after tumor resection. Using the above data, in conjunction with quantitative filtering, we were able to select seven potential platelet-derived biomarkers of early-stage cancer. This pioneering study on the platelet proteome in cancer patients clearly identifies platelets as a new source of protein biomarkers of early-stage cancer.