Cytogenetic analysis of an aggressive angiomyxoma of the vulvar region of a 16-year-old female revealed loss of one X chromosome (45,X,-X) in eight of 20 metaphase cells analyzed. Fluorescence in situ hybridization (FISH) performed on disaggregated cells from paraffin embedded lesional tissue confirmed loss of an X chromosome in 31% of cells. Cytogenetic analysis performed on peripheral blood showed a normal chromosomal complement (46,XX). Thus, loss of one X chromosome appears to be confined to the neoplasm. This anomaly has not been previously described in aggressive angiomyxoma.