We report on the cases of two sisters with carotid body tumor (CBT) and present a literature review that assembles epidemiologic information on 88 familial and 835 nonfamilial CBT patients. The sex ratio (males/females) of 1.0 for familial CBT (0.7 for nonfamilial) and CBT reports with complete sibship information suggest autosomal dominant genetic transmission. As in other familial cancers, bilateral disease is significantly more frequent in familial (31.8% of cases) than in nonfamilial CBT (4.4%). However, there is no difference in age at diagnosis between familial and nonfamilial CBR. Thus, this adult-onset familial cancer does not completely fit the Knudson "two-step mutation" model of carcinogenesis. We also found that 6% of reported CBT patients developed second primary tumors, mostly other paragangliomas. This feature suggests that CBT may be part of a larger neurocristopathy syndrome of multiple tumors of cells of neural crest origin.