We present the prenatal diagnosis of a chromosome 11q14.3–q22.1 deletion identified in three generations without apparent phenotypic consequences. A 25-year-old G2, P1 woman underwent amniocentesis at 15 weeks' gestation because of a positive result for Down syndrome maternal serum-screening test (1/70). The fetal karyotype revealed an interstitial deletion of the long arm of chromosome 11 confirmed by CGH and FISH: 46,XX,del(11)(q14.3q22.1). The mother and grandfather of the fetus presented the same interstitial deletion with a little if any phenotype effect. The pregnancy was carried to term and resulted in the birth of a normal girl. To our knowledge, only one case of a chromosome 11q14.3–q21 deletion without phenotypic anomalies has been reported. Our study allows the initially described haplosufficient region to be extended from 3.6 Mb to at least 8.5 Mb. This large deletion was compatible with fertility and apparently normal phenotype. Identification of such chromosomal regions is important for prenatal diagnosis and genetic counseling. © 2008 Wiley-Liss, Inc.