Disseminated bacillus Calmette-Guérin infection (BCGitis) is an uncommon condition which is usually associated with primary immunodeficiency. Skin histopathology findings have been described in rare cases only. A retrospective clinicopathological study was performed to assess the potential utility of skin biopsies in the diagnosis, prognosis and follow-up of these patients. Four cases of disseminated BCGitis in children with Severe Combined ImmunoDeficiency were biopsied before and after Haematopoietic Stem Cell Transplantation (HSCT). The results were compared to the clinical and immunological status of the children. Early skin biopsies revealed either dense dermal infiltration by foamy macrophages filled with acid fast bacilli (AFB) or mycobacterial spindle-cell pseudotumors rich in AFB. There were no granulomas. These patterns led to the diagnosis of disseminated BCGitis potentially caused by severe immunodeficiency. After HSCT, repeated skin biopsies were performed on persistent or new cutaneous lesions to rule out immune reconstitution inflammatory syndrome and to check for tuberculoid granulomas. One patient died of BCGitis combined with graft versus host disease. The 3 others presented with progressive-onset well differentiated granulomas over a long period and recovered. Skin biopsy is a useful part of the diagnostic workup for disseminated BCGitis, directing the clinician toward severe immunodeficiency. Moreover, skin biopsy may be a useful means of monitoring immune restoration for prognostic purposes.