The association of Kaposi's sarcoma (KS) with second primary cancers, especially of the lymphoreticular system, has been frequently noted. To confirm these reports in a systematic way, data on a series of 92 patients with KS treated at Memorial Sloan-Kettering Cancer Center (MSKCC) 2949-1975 were subjected to extensive statistical analysis. Use was made also 4517 double primaries including all sites, diagnosed at MSKCC 1949-1974, and 1959 simultaneous double primaries from the Third National Cancer Survey. Some key results: (1) of KS patients had toher primary malignancies; (2) there was a 20-fold increase in the incidence of lymphoreticular malignancies after diagnosis of KS; (3) in the MSKCC series double primaries, lymphoreticular malignancies were involved in 8% of cases; for KS alone the corresponding figure was 58%. Our findings provide evidence in support of possible etiopathogenic mechanisms that may be involved in the natural course of KS.