The location of genes involved in tumor evolution has been inferred from experiments in which loss of constitutional heterozygosity has been detected in tumor DNA at high frequency in specific chromosome regions. For example, cytogenetic and molecular abnormalities on chromosome 1p have been reported in tumors such as malignant melanoma and neuroblastoma which arise in cells derived from embryonic neural crest tissue. To extend these observations, we have examined tumor DNA from three cases of Merkel cell carcinoma for evidence of loss of constitutional heterozygosity on the short arm of chromosome 1. In all three cases, heterozygous allelic deletions of varying extent on distal chromosome 1p were detected in tumor DNA. Comparisons with neural crest tumors suggest that loss of heterozygosity on distal chromosome 1p in Merkel cell tumors may be a marker of neural crest origin.