Rituximab is one of the monoclonal antibodies that is used in the management of malignancies and auto-inflammatory disorders. Rituximab causes Hypersensitivity Reactions (HSRs) during infusions. The delay of treatment or loss of a highly efficient drug can be prevented by rapid drug desensitization method in patients who are allergic to rituximab. Although HSRs and desensitization protocols to mAbs have been well described in adults, the experience in the paediatric population is very limited. To best of author's knowledge, this is the first case series describing a novel, rapid desensitization protocol against rituximab hypersensitivity in two teenagers with high-grade B cell non-Hodgkin's lymphoma and steroid-resistant minimal change disease who developed hypersensitivity to rituximab. Here, authors present case reports of two patients who were desensitized successfully by using novel rapid desensitization protocol for rituximab.