Only one oncogene, cyclin D1/PRAD1, has an established role in parathyroid tumorigenesis, and parathyroid tumor suppressor genes on chromosome arms 1p and 11q, which still have not been identified, have also been implicated by loss of heterozygosity analysis. To investigate whether other putative tumor suppressor genes are involved in the pathogenesis of parathyroid adenomas, we performed a more comprehensive analysis of allelic losses in these tumors. Using 39 polymorphic markers, we examined each chromosome arm, excluding the short arms of the acrocentric chromosomes. In 25 parathyroid adenomas, frequent loss of heterozygosity, in > 25% of the informative cases, was observed on chromosome arms 6q (30%), 11p (27%), and 15q (35%), in addition to previously reported 1p (30%) and 11q (38%) allelic losses. To more specifically localize the smallest shared regions of molecular genetic deletion, we examined the following chromosomes in greater detail: chromosome 6 (9 additional markers), chromosome 11 (8 additional markers), and chromosome 15 (15 additional markers). The regions most commonly deleted in these tumors were 6q22-23, 6q26-27, 11q13, 15q11-21, and 15q26-qter. All tumors with 11p loss had patterns consistent with monosomy for chromosome 11. These findings provide novel evidence for the existence of tumor suppressor genes on chromosome arms 6q and 15q that contribute commonly to the pathogenesis of parathyroid adenomas.