In this introductory chapter a story has been reviewed concerning the evolution of the concept of "cancer and thrombosis", since its first description by Armand Trousseau in 1865. From scattered reports on experimental material (tumor extracts) or on animal models of tumor/metastasis growth, through the progress of cell biology and experimental pharmacology, during the last 20 years interest has moved to clinical questions, such as: how to prevent and treat thrombosis, a frequent complication of both solid and hematologic malignancies? Has an occult cancer to be suspected in the majority of cases of idiopathic deep vein thrombosis? Do we need to prevent pharmacologically the occurrence of chemotherapy-associated thrombosis? Do anticoagulants have an impact on the natural history of some tumors? Why antiangiogenetic agents may be associated to a thrombotic risk? Presently, a continuous cross-talk between clinical results and experimental data is required to provide answers to these questions, taking advantage of a multidisciplinary approach to this old but still partially mysterious issue.