A second primary cancer (SPC) is a new primary cancer developing in a person with a history of cancer in a new site or tissue and subsequent to the initial cancer. Advances in cancer treatment have led to marked improvements in cancer cure rates over the past 30 years, and the control of risk factors has further increased longevity. Still, cancer survivors are at increased risk not only for recurrence of the primary cancer but also for the development of second primary malignancies, the latter being especially true for survivors of childhood cancer. SPCs are now more common, and research into them has intensified. This monograph provides a synthesis of the current research on SPC, culminating in pertinent summary charts, covering the whole spectrum of first and second primary cancers and the association between them. Readers will gain a general understanding of the epidemiology and of the excess risk of SPCs following an implicated first malignancy. The known or suspected etiologic factors for SPCs are identified, and the field is further narrowed to those factors that are modifiable in practice. Effective preventive measures that might reduce the burden of SPC, both for individuals and across at-risk populations, are presented. Providing practical guidance in terms of possibilities and priorities, this monograph will be a valuable tool for oncologists, general practitioners and health administrators.