Second primary cancers were studied in persons with rare tumors between 1943 and 1980. The risk of developing a new cancer was evaluated in 7,211 persons with cutaneous melanoma, 1,784 persons with eye cancer, 10,273 persons with tumors of the brain and nervous system, 1,935 persons with thyroid cancer, 1,542 persons with bone tumors, and 2,318 persons with malignant neoplasms of the connective tissue. All cancer patients were diagnosed in Denmark between 1943 and 1980 and survived for 2 or more months. Nonmelanoma skin cancers were excluded from the analysis, whereas tumors of the brain and nervous system included both benign and malignant neoplasms. Overall, patients with these cancers showed no greater incidence of new tumors than expected from comparisons with the general population. An excess of chronic lymphocytic leukemia was observed subsequent to all cancers derived from the neural tube, i.e., melanoma and tumors of the eye, brain, and nervous system. Bone cancer occurred excessively, although the possibility of misclassified metastases could not be eliminated. Patients with tumors of the brain and nervous system who survived for 10 or more years developed significantly more cancers of the kidney and connective tissue and melanoma than anticipated. A deficit of second cancers of the digestive system was noted after primary bone and connective tissue cancers, in contrast to an excess of second cancers of the lung and kidney. Although based on few cases, patients with bone cancer showed a large excess of eye cancer as a second primary. The association between cancers of the breast and connective tissue was found to be bidirectional. Persons with connective tissue cancer were at increased risk of developing non-Hodgkin's lymphoma. Thyroid cancer patients were at high risk of subsequent tumors of the brain and nervous tissue and non-Hodgkin's lymphoma. However, contrary to previous reports, the risk of breast cancer was not elevated following thyroid cancer.