Among 4,869 patients with chronic lymphocytic leukemia (CLL) from the series of the End Results Program of the National Cancer Institute, Bethesda, Maryland, second primary cancers developed in 234 patients, compared to 204.9 expected. The risk was significantly elevated for malignant melanoma, soft-tissue sarcomas, and lung cancer. The frequency of rectal cancer was also elevated, but not significantly. The excess risk for these specific sites persisted throughout the period of follow-up, suggesting a susceptibility state that complicated the leukemic process rather than suggesting methodologic, diagnostic, or therapeutic effects. Immunologic defects to CLL may be involved in the etiology of excess risk for these sites, because a similar array of nonlymphoid tumors was seen following therapeutic immunosuppression among renal transplant recipients.