Loss of heterozygosity (LOH) at chromosome 11q13 loci has been described in the majority of larger parathyroid tumors from patients affected by Multiple Endocrine Neoplasia type 1 (MEN 1) syndrome. Since classical histology of the whole parathyroid gland does not permit a clear morpho-genetic correlation, the clonal composition of abnormal parathyroid tissue was analyzed in DNA obtained from single nodules and non-nodular areas within MEN 1 parathyroid lesions. Microdissected sections were analyzed by chromosome 11q13 microsatellite-PCR for LOH and by patterns of X-inactivation. We detected LOH for chromosome 11q13 loci in at least one microdissected area for each familial MEN 1 patient, but not in the single sporadic case. X-inactivation pattern of two "clonal" tumors exhibited a polyclonal cell composition of these microdissected samples, indicating the existence of a genetic heterogeneity in MEN 1 parathyroid microareas exhibiting a "clonal" pattern for allelic losses.