Updated project metadata. Platelets play an important role in primary hemostasis, inflammation , (tumor) angiogenesis and cancer metastasis. Platelets are produced by megakaryocytes in the bone marrow and contain numerous bioactive proteins (e.g. growth factors, chemokine’s and proteases). These proteins inside platelets are either synthesized by the parental megakaryocytes or absorbed from the (micro)circulation. Therefore, it was postulated that changes in platelet protein content might indicate the presence or recurrence of a malignant tumor. We followed up the notion that both cancer and cancer therapy affect the platelet proteome. The aim of the current study was 1) to identify a pan-cancer proteome signature that could be used to discriminate patients with cancer from healthy individuals, and 2) to investigate the effect of cancer therapy on the platelet proteome. In this study, we included patients with cancer and healthy controls. Using global protein profiling by mass spectrometry-based proteomics we determined that the platelet proteome is affected by both cancer presence and antitumor therapy.