[en] One of the most important complications associated with bone marrow transplantation (BMT) is graft-versus-host reaction (GVHR) altering different organs. The immunosuppressive regimen frequently abates the severity of cutaneous lesions to a peculiar lymphocyto-depleted GVHR (LD-GVHR) with scant recognizable inflammatory cells and almost absence of epidermal injury. The recently revisited histological criteria for cutaneous GVHR are of little help in diagnosing such LD-GVHR. As calprotectin (L1-protein) has been reported to be expressed in several types of stressed epithelia, we assessed the epidermal calprotectin expression during LD-GVHR. Calprotectin expression was studied by immuno-histochemistry using the Mac 287 moAb in 50 cases of LD-GVHR and 40 cases of toxic reactions due to the conditioning regimens or to post-transplant drugs. Calprotectin was evidenced in normal looking keratinocytes of all cutaneous LD-GVHR cases and in the vast majority of cytotoxic drug-induced dermatitis. It is concluded that calprotectin immunoreactivity appears to be a diagnostic clue in LD-GVHR. The epidermal calprotectin expression occurs early in GVHD, irrespective of the histological grading. However, it cannot be used alone to distinguish early LD-GVHR from drug-induced dermatitis.