Rhabdoid tumor is a rare malignant neoplasm of childhood that may occur in various locations, including the central nervous system and the kidney. Previous cytogenetic studies of primary rhabdoid tumors have demonstrated monosomy or deletion of chromosome 22 and have implicated the presence of a rhabdoid tumor suppressor gene that maps to 22q. We have employed fluorescence in situ hybridization to narrow the region for this locus in four rhabdoid tumor cell lines with translocations or deletions involving chromosome segment 22q11. The completion of a cosmid and yeast artificial chromosome contig spanning the immunoglobulin lambda gene locus to BCR has allowed us to map a critical region for a rhabdoid tumor gene to a 500 kb span of chromosome segment 22q11.