Relapsed/refractory paediatric T-ALL carries a dismal prognosis and newer therapy options are urgently needed. Daratumumab, an antibody to transmembrane protein CD38 expressed on T-cells, is currently under investigation as a targeted immunotherapy approach to T-ALL. A 2-year-old male with refractory T-ALL received off-label, monotherapy with daratumumab, resulting in a rapid partial response with minimal toxicity. This is the first documentation of daratumumab administered to a child with this indication, and supports its potential benefit in T-ALL.