Sarcoma (OS), the most common malignant primary bone tumor, typically occurs during the adolescent growth spurt. Our series of descriptive studies have detailed OS incidence in the U.S. and around the world. Our pooled analysis showed that individuals in the highest birth weight category and those taller than average had an increased risk of OS compared with controls derived from the 2000 US National Center for Health Statistics Growth Charts. Our work to discover the genetic risk factors for OS have utilized a prospective case-control study initiated in 1995 with the NCI and Harvard Dental School. Previously we found several SNPs in DNA repair, cell cycle, and growth-related genes associated with OS risk. We recently conducted an international collaborative genome-wide association study (GWAS) aimed at identifying genetic risk factors for OS. We are working closely with the Children’s Oncology Group, and ten institutions in Europe, Canada, the U.S., Brazil, and Australia. This study identified SNPs in GRM4, and 2p25.2 associated with OS risk. A replication GWAS, fine mapping of risk loci, and somatic sequencing of tumor tissue are underway.