The third reported case of Ewing's sarcoma in siblings is presented. All reported siblings to date have been female. Because of the most unusual occurrence, clues for environmental and genetic factors in the origin of the tumors were sought. Human leukocyte antigen (HL-A) genotyping, routine chromosomal, and prophase chromosomal studies were obtained. Despite extensive study, the existence of an infectious agent, exposure to a carcinogen, or genetic abnormality could not be defined.