Abstract Severe combined immunodeficiencies (SCIDs) are a heterogeneous group of diseases characterized by profound compromise of both T lymphocyte and B lymphocyte numbers and/or function. From a descriptive standpoint, SCID can be categorized based on the composition of the peripheral blood lymphocyte populations observed in affected patients. While many forms of SCID present with both T cell and B cell lymphopenia (T−B− SCID), in one group of such disorders B cell differentiation is conserved and normal or even elevated numbers of peripheral blood B lymphocytes can be observed. These diseases are called SCID T−B+ and include the X-linked form of SCID (SCIDX-1), the deficiency of Janus kinase family member 3 (JAK3-SCID), and the defect of expression of the alpha chain of the interleukin-7 receptor (IL7-Rα-SCID). This article describes the main features of these rare clinical entities.