Uterine leiomyoma with massive lymphoid infiltration is a rare morphologic phenomenon. We describe the first case of uterine leiomyoma with lymphoid infiltration observed in a patient after chemotherapy for sigmoid cancer. We performed immunohistochemical analysis with a panel of antibodies to several markers. Detection of CD20, CD3, Ki67, CD68 and Epstein-Barr virus nuclear antigen assisted in the differential diagnosis and partial elucidation of the pathogenesis. In addition, we examined the lysosome-associated membrane proteins LAMP-1 and LAMP-2 for the first time in this lesion. Their expression was elevated, indicating enhanced autophagy, an indirect sign of degenerative changes in this benign tumor characterized by massive lymphoid infiltration.