Increasing incidences of cancer of unknown primary (CUP) have been observed in Sweden previously. However, it is not known how the incidence trends for specific locations of metastasis vary. Site-specific data are available on the basis of the ninth international classification of diseases. CUP patients were identified between 1987 and 2008 from the Swedish Family-Cancer Database. Malignant neoplasms of ill-defined sites were diagnosed in 4042 patients, 1976 developed metastasis in lymph nodes, 9615 had metastasis in specified organs, and in 8052 patients, the malignant neoplasm was diagnosed without further specification. Age-standardized incidence rates for 23 685 patients were analyzed using a direct method of standardization. Overall, the incidence of CUP decreased from 6.98 to 6.00 per 100 000 from 1987 to 2008. The number of patients diagnosed with metastasis in specified organs decreased, whereas the number of patients diagnosed with CUP without further specification increased from 2.65 to 3.02 per 100 000. With improvements in diagnostic methods and imaging techniques for identification of cancer, the incidences of CUP have been decreasing because primary tumors can be specified more often. Computed tomography is typically sensitive in detecting lung, kidney, and colorectal cancers, which are known to have a genetic link with CUP. Prostate-specific antigen testing is used to detect prostate cancer, for which bone is a common metastatic site. Liver metastases are common if the primary tumor is located in the colorectum. If the primary tumor is found, this cancer site replaces the diagnosis of CUP within the Cancer Register and therefore CUP incidence is decreased.