Common variable immunodeficiency (CVID) is the second most common immunodeficiency and may be classified according to the presence or absence of mature B-cells, the latter subgroup being exceedingly rare. We describe a 66-year-old patient who over six months developed profound hypogammaglobulinemia associated with a complete absence of circulating B-lymphocytes and had a fatal outcome. Immunophenotypic analysis of a bone marrow aspirate demonstrated a strongly reduced number of B-cell precursors (CD34+/CD19+) but normal numbers of CD34+/CD45+ hematopoietic progenitor cells. This case is remarkable with respect to its documented rapid evolution. Possible triggers are discussed, a combination of drug toxicities being the most likely.