Carney complex is an inherited tumor syndrome consisting of spotty skin pigmentation, myxomatosis, schwannomas, and endocrine tumors. Linkage analysis has identified 2p16 and 17q22–24 as likely chromosomal loci to harbor genes causing Carney complex. The authors recently identified mutations in the PRKAR1A gene as being responsible for the disease in kindreds mapping to 17q. Inactivating mutations of this gene, which codes for the type 1A regulatory subunit of protein kinase A, lead to dysregulation of protein kinase A function in tumors from patients with Carney complex. Although the causative gene has not yet been located at 2p, this locus also appears to be involved in the molecular pathogenesis of Carney complex, because patient tumors often demonstrate multiple genetic changes in this region. Despite the known genetic heterogeneity in the disease, clinical analysis has not detected any corresponding phenotypic differences between patients with PRKAR1A mutations and those without.