We report 3 unique cases of extensive myometrial infiltration by foamy histiocytes in uteri removed for benign conditions. The histologic findings were similar and consisted of diffuse infiltration of myometrium by clusters, cords, and sheets of CD163-positive histiocytes with no other significant inflammatory cell component. Most of the histiocytes had pale, vacuolated, or foamy cytoplasm, but in 1 case eosinophilic granular cytoplasm was also present. In all cases, the nuclei were small and eccentric. No mitotic figures were identified. All cases involved young, parous women who had remote prior surgical interventions involving the uterus; 2 patients had a prior cesarean section and 1 had a prior therapeutic abortion. There was no associated neoplastic or infectious condition in any of the cases, and no patient had a prior history of pelvic inflammatory disease. Although we were unable to obtain more detailed obstetric history, an exuberant and persistent reaction to the surgical procedure and/or to a carrier substance for uterotonic intramyometrial injection may be the basis for this unusual reaction, which we designate as myometrial xanthomatosis.