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Time trends in incidence, causes of death, and prognosis of cancer of unknown primary (CUP) could provide important clues for occult primary sites and thus result in effective organ-specific treatment, although such studies are seldom reported. We aimed at examining time trends in percentage and incidence rates, causes of death, and survival of CUP. A total of 50 545 patients with CUP were identified in the Swedish Cancer Registry from 1960 to 2008. We used direct standardization to standardize age-adjusted incidence rate to the Segi world population. Consistent increase before the late 1990s and dramatic decrease afterward was observed for both percentage and incidence of CUP in Swedes regardless of sex. Comparable time trends were noted in Norwegian and Finnish populations, but with several years earlier peaking times. For most anatomic sites, CUP and lung cancer were the two most common causes of death for patients with CUP irrespective of nodal involvement. Survival probability at 12 months after CUP was approximately 20% and then leveled off at approximately 10%. Adenocarcinoma accounted for most of this incidence variation and experienced the worst prognosis. High incidence rates and comparable time trends for CUP were observed in Sweden, Norway, and Finland. The increasing time trends may partially reflect the change of autopsy rates in these countries. The decreased incidence in the last decade could be due to an increasing identification of unknown primary caused by improving diagnostic methods. Histological types were significantly associated with survival in patients with CUP.