Uterine leiomyoma (UL) is a benign, smooth muscle tumor of the uterus affecting a significant proportion of women of reproductive age. Deletions involving chromosome 7q22 are common in UL and vary in length. Previously reported 7q22 deletion intervals were physically mapped using information from the recently completed human genome sequence. Four distinct deletion intervals, which included a microdeletion reported by our laboratory, were identified. This microdeletion contains two known genes, ORC5L and LHFPL3. The single deleted marker in the microdeletion was mapped within the LHFPL3 locus. The ORC5L gene has been studied in UL. Conversely, LHFPL3 has been annotated only recently, and has therefore not been studied in UL. The predicted LHFPL3 protein sequence contained a polyalanine domain, and a signature sequence for the PMP22 Claudin protein family. Members of this family are transmembrane proteins with roles in differentiation, proliferation, and extracellular matrix formation, and have been implicated in other tumors. Differences in LHFPL3 expression were observed in both human and Eker rat UL. Our results provide evidence for four distinct 7q22 deletion intervals, each with multiple candidate genes, including the recently identified LHFPL3 gene.