Targeted therapies are increasingly used in the management of pediatric low grade glioma. How-ever for patients who show resistance to these treatments, limited options are available. We pre-sent the case of a patient with BRAFV600 mutated low grade glioma who showed progression on a combination of trametinib and dabrafenib. Discontinuation of treatment was associated with a life-threatening deterioration and reintroduction of targeted therapy had no effect. The patient eventually showed a dramatic response to TPCV (thiguanine, procarbazine, CCNU and vincris-tine) , which suggests a role of chemotherapy in these situations.