Genomic imprinting is an epigenetic modification of the gamete or zygote leading to parental origin-specific gene expression in somatic cells of the offspring. We have previously identified a cluster of imprinted genes on human chromosome 11p15.5, a region involved in Beckwith-Wiedemann syndrome, Wilms' tumor, and ovarian, breast, and lung cancer. Here we show that TSSC3, which is homologous to the mouse apoptosis gene TDAG51 and maps to this region, is imprinted and expressed from the maternal allele in normal development. This result is important for three reasons: (a) TSSC3 is the first apoptosis-related gene in any species found to be imprinted; (b) it is located within the tumor suppressor region of 11p15; and (c) it lies within 15 kb of the nonimprinted gene hNAP2, thus defining a small boundary interval between imprinted and nonimprinted genes on 11p.