The authors address the perceived but undocumented notion that only approximately one-third of individuals who are homozygous for type 1 Gaucher disease (GD) mutations, particularly Ashkenazi Jewish N370S homozygotes, are symptomatic and come to medical attention. Prenatal carrier screening of over 8000 Ashkenazi Jewish adults revealed a carrier frequency of 1:15 and 9 previously undiagnosed GD homozygotes (1 in 897). Because these homozygotes have never been systematically studied, they evaluated 37 “asymptomatic” type 1 GD individuals who were serendipitously identified by their or other prenatal carrier screening programs in New York City. Clinical, laboratory, and radiologic studies revealed that all patients had disease manifestations ranging from mild to severe, and, in particular, all had bone involvement that progressed with age in many homozygotes, often requiring therapeutic intervention. These findings indicate that homozygosity for the common N370S mutation does not result in a benign or low penetrant disease and emphasizes the importance of early recognition and appropriate management to minimize or prevent future irreversible disease complications.