Gaucher disease type 1 (GD1) is the most common lysosomal storage disease and affects nearly 1 in 40,000 live births. In addition, it is the most common genetic disorder in the Ashkenazi Jewish population with phenotypic variation presenting in early childhood to asymptomatic nonagenarians. There have been a number of studies showing an increased risk of certain malignancies in patients, especially non- Hodgkin's lymphoma (NHL) and multiple myeloma. We describe a 66-year-old Ashkenazi Jewish male with GD1 who was first started on enzyme replacement therapy (ERT) with imiglucerase for GD1 at age 57 years, followed a year later by the diagnosis of diffuse large b-cell non-Hodgkin's lymphoma (DLBCL). He was treated with R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone, plus the monoclonal antibody rituximab), however relapsed and developed myelodysplasia necessitating an allo-stem-cell transplantation but succumbed to severe graft vs. host disease. In addition, we also describe a 38-year-old Ashkenazi Jewish male with GD1 who was diagnosed with DLBCL at age 22 years with Gaucher disease diagnosed on pre-treatment bone marrow biopsy which was confirmed by enzyme assay and genotyping. At age 24 years, he was started on ERT with imiglucerase and at age 35 years, he switched to eliglustat. He has remained in remission from the lymphoma. A meta-analysis of the literature will be elaborated upon and we will discuss the relationship of GD1 to NHL and discuss more recent information regarding lyso-GL1 and the development of NHL and multiple myeloma.