Cancer patients have a 20% higher risk of new primary cancer compared with the general population. Approximately one third of cancer survivors aged >60 years were diagnosed more than once with another cancer. As the number of cancer survivors and of older people increases, occurrence of multiple primary cancers is also likely to increase. An increasing interest from epidemiologic and clinical perspectives seems logical. This chapter begins with the risk pattern of multiple cancers in the population of a developed country with high survival rates. Multiple cancers comprise two or more primary cancers occurring in an individual that originate in a primary site or tissue and that are neither an extension, nor a recurrence or metastasis. Studies of multiple cancers have been mainly conducted in population-based settings, and more recently in clinical trials and case control studies leading to further understanding of risk factors for the development of multiple primary cancers. These factors include an inherited predisposition to cancer; the usual carcinogenic or cancer-promoting aspects of lifestyle, hormonal, and environmental factors; treatment of the previous primary cancer; and increased surveillance of cancer survivors. Finally, implication on research strategies and clinical practice are discussed, covering the whole range of epidemiologic approach.